{"gene":"KAT2B","run_date":"2026-06-10T01:55:23","timeline":{"discoveries":[{"year":1999,"finding":"PCAF acetylates p53 in vitro at lysine K320, a residue distinct from that acetylated by p300, and this acetylation increases p53's ability to bind its cognate DNA site. Acetylation at this site is detected in vivo and increases in response to DNA-damaging agents.","method":"In vitro acetyltransferase assay, site-specific acetylation antibodies, in vivo detection after DNA damage","journal":"Molecular and cellular biology","confidence":"High","confidence_rationale":"Tier 1 / Strong — in vitro enzymatic assay with site identification, validated in vivo with specific antibodies, independently replicated across multiple studies","pmids":["9891054"],"is_preprint":false},{"year":1997,"finding":"PCAF directly interacts with MyoD and forms a multimeric complex with p300/CBP on promoter elements to drive myogenic differentiation; the histone acetyltransferase activity of PCAF (but not p300) is required for p21 expression and terminal cell-cycle arrest during myogenesis.","method":"Anti-PCAF antibody microinjection, exogenous expression, reporter assays, HAT-dead mutant analysis","journal":"Molecular cell","confidence":"High","confidence_rationale":"Tier 2 / Strong — loss-of-function (antibody microinjection), gain-of-function, and HAT mutant experiments all converge on same conclusion","pmids":["9659901"],"is_preprint":false},{"year":1998,"finding":"PCAF directly associates with the DNA-binding domain of nuclear receptors (RXR/RAR heterodimer) in a ligand-dependent manner and independently of p300/CBP, defining a novel cofactor interaction surface on nuclear receptors.","method":"Ligand-dependent recruitment from mammalian cell extracts, in vitro direct binding assay, transcription reporter assays","journal":"Genes & development","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct binding shown in vitro and in cell extracts with ligand-dependence confirmed; single lab","pmids":["9620851"],"is_preprint":false},{"year":1999,"finding":"Adenoviral E1A directly binds PCAF independently of CBP and inhibits PCAF HAT activity in vitro, blocking nucleosomal histone modification by the PCAF complex and p53 acetylation.","method":"In vitro HAT assay, direct binding assay, in vivo transcription assays","journal":"Cell","confidence":"High","confidence_rationale":"Tier 1 / Strong — direct in vitro enzymatic inhibition demonstrated, replicated across labs (also PMID:9687513)","pmids":["10025405","9687513"],"is_preprint":false},{"year":1998,"finding":"PCAF forms a ternary complex with p300 and HIV-1 Tat in cells, and the HAT activity of PCAF (but not p300) is specifically required for Tat transactivation of integrated (but not unintegrated) HIV-1 LTR.","method":"Co-immunoprecipitation (ternary complex), dominant-negative HAT mutant transfection, integrated vs. unintegrated LTR reporter assays","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal co-IP plus HAT-dead mutant dissection of integrated vs. episomal LTR, mechanistically rigorous","pmids":["9733796"],"is_preprint":false},{"year":2000,"finding":"Mouse Notch1 intracellular region (RAMIC) directly interacts with mouse PCAF (and GCN5) through its ankyrin repeats and transactivation domain, recruiting PCAF to RBP-J and facilitating RBP-J-mediated transactivation; the N-terminal regions of PCAF/GCN5 are required for this interaction.","method":"Co-immunoprecipitation, domain mapping, transactivation reporter assays, E1A and Twist inhibition","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — co-IP domain mapping and functional reporter assays in single lab","pmids":["10747963"],"is_preprint":false},{"year":1998,"finding":"Human GCN5 and P/CAF have extended homologous amino-terminal domains enabling acetylation of nucleosomal substrates (not only free histones), unlike the shorter yeast Gcn5p; both interact with CBP/p300 and display similar substrate specificities for histone H3.","method":"In vitro HAT assay with nucleosomal and free histone substrates, protein interaction assays, immunodetection","journal":"Molecular and cellular biology","confidence":"High","confidence_rationale":"Tier 1 / Strong — reconstituted in vitro HAT assay with nucleosomal substrates, comparative domain analysis","pmids":["9742083"],"is_preprint":false},{"year":2000,"finding":"Kinetic mechanism of human P/CAF follows a fully ordered Bi-Bi mechanism: acetyl-CoA binds first to free enzyme (Kd = 0.64 µM), then histone H3 peptide binds; chemical catalysis (acetyl transfer to Lys-14 of H3) is rate-determining; Glu-570 is the proposed general base catalyst.","method":"Bi-substrate kinetic analysis, product inhibition, equilibrium dialysis, pre-steady-state quench-flow, pH-dependent activity measurements","journal":"Biochemistry","confidence":"High","confidence_rationale":"Tier 1 / Strong — rigorous multi-method in vitro mechanistic enzymology establishing catalytic mechanism","pmids":["11009610"],"is_preprint":false},{"year":2003,"finding":"P/CAF auto-acetylates itself intramolecularly at five lysines (416–442) within its nuclear localization signal (NLS) at the C-terminus, and intermolecularly via its N-terminal domain; P/CAF is also acetylated by p300 but not CBP; auto-acetylation increases PCAF HAT activity.","method":"In vitro acetylation assay, mutational analysis, in vivo acetylation detection","journal":"Nucleic acids research","confidence":"Medium","confidence_rationale":"Tier 1 / Moderate — in vitro assay with mutagenesis, single lab, no independent replication cited","pmids":["12888487"],"is_preprint":false},{"year":2008,"finding":"P/CAF autoacetylation at the NLS (C-terminal lysines) controls its nuclear localization; HAT-inactive P/CAF accumulates in the cytoplasm; HDAC3 (and to a lesser extent HDAC1/2/4) deacetylates P/CAF leading to cytoplasmic accumulation; P/CAF accumulates in cytoplasm during apoptosis.","method":"Subcellular fractionation, fluorescence microscopy, HAT-dead mutant, HDAC overexpression/knockdown","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct localization by imaging and fractionation with functional mutant analysis, single lab","pmids":["19015268"],"is_preprint":false},{"year":2006,"finding":"PCAF interacts physically with PTEN and acetylates PTEN at Lys125 and Lys128 within its catalytic cleft in a growth-factor-dependent manner, reducing PTEN's lipid phosphatase activity and thereby maintaining PI3K/AKT signaling; acetylation-resistant K125R/K128R mutants retain PI3K-suppressing and G1 arrest activities even with PCAF overexpression.","method":"Co-immunoprecipitation, in vitro acetyltransferase assay, shRNA knockdown, acetylation-resistant mutant analysis, cell cycle assays","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1–2 / Moderate — in vitro acetylation, acetylation-site mutagenesis with functional readout, shRNA rescue, single lab but multiple orthogonal methods","pmids":["16829519"],"is_preprint":false},{"year":2007,"finding":"PCAF possesses an intrinsic ubiquitin E3 ligase activity (distinct from its acetyltransferase activity) that ubiquitinates Hdm2, promoting its degradation and thereby stabilizing p53; PCAF knockdown stabilizes Hdm2.","method":"PCAF knockdown in HeLa/U2OS cells, in vitro ubiquitination assay, domain deletion analysis","journal":"Nature cell biology","confidence":"High","confidence_rationale":"Tier 1–2 / Strong — in vitro ubiquitination assay plus cellular knockdown phenotype, mechanistically distinct activity characterized","pmids":["17293853"],"is_preprint":false},{"year":2002,"finding":"PCAF acetylates HIV-1 Tat at Lys50; acetylated Tat binds the PCAF bromodomain; structural analysis defined critical interaction residues (Y47/R53 in Tat; V763/Y802/Y809 in PCAF bromodomain); mutations at these residues cumulatively inhibit Tat–PCAF interaction and synergistic HIV promoter activation.","method":"In vitro binding assay, in vivo co-immunoprecipitation, structural analysis of acetyl-peptide–bromodomain complex, site-directed mutagenesis, HIV promoter reporter assay","journal":"The EMBO journal","confidence":"High","confidence_rationale":"Tier 1 / Strong — structural data plus mutagenesis plus functional reporters; multiple orthogonal methods","pmids":["12032084"],"is_preprint":false},{"year":2000,"finding":"P/CAF directly interacts with Smad3 (via Smad3 MH2 domain and P/CAF N-terminal region) upon TGF-β receptor activation; P/CAF potentiates TGF-β/Smad3-mediated transcription cooperatively with p300 and Smad4.","method":"In vitro GST pull-down, co-immunoprecipitation in mammalian cells, transcription reporter assays","journal":"Nucleic acids research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal in vitro and in vivo binding plus functional reporters, single lab","pmids":["11058129"],"is_preprint":false},{"year":2000,"finding":"P/CAF-mediated acetylation of TAL1/SCL maps to a lysine-rich motif in the loop region and increases TAL1 DNA binding while selectively inhibiting its interaction with co-repressor mSin3A; an acetylation-defective P/CAF mutant inhibits TAL1 acetylation, DNA binding, transcription, and terminal erythroid differentiation.","method":"In vitro acetylation assay, domain mapping, DNA-binding EMSA, co-immunoprecipitation, differentiation assay with HAT-dead mutant","journal":"The EMBO journal","confidence":"High","confidence_rationale":"Tier 1–2 / Strong — in vitro enzymatic assay, site mapping, EMSA, co-IP, and cell differentiation phenotype all converge","pmids":["11118214"],"is_preprint":false},{"year":2000,"finding":"Mice lacking PCAF are developmentally normal; in PCAF-null mice, PCAF-B/GCN5 protein levels are drastically elevated in tissues where PCAF is normally abundant, indicating functional compensation between PCAF and GCN5.","method":"Gene knockout mouse model, Western blot quantification of compensatory protein levels","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 2 / Strong — clean knockout genetic model with biochemical compensation measured in multiple tissues","pmids":["11027331"],"is_preprint":false},{"year":2001,"finding":"Cyclin D1 and the androgen receptor (AR) both bind overlapping domains of P/CAF; cyclin D1 displaces AR binding to P/CAF in vitro; the HAT activity of P/CAF rescues cyclin D1-mediated AR trans-repression.","method":"In vitro binding/displacement assay, HAT-dead P/CAF rescue experiment, reporter assays","journal":"Molecular endocrinology (Baltimore, Md.)","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — in vitro competitive binding plus HAT-dead rescue in reporter assays; single lab","pmids":["11328859"],"is_preprint":false},{"year":1999,"finding":"Cyclin D1 interacts with the histone acetyltransferase P/CAF, facilitating P/CAF–estrogen receptor (ER) association; P/CAF potentiates cyclin D1-stimulated ER transcriptional activity in a dose-dependent, HAT-activity-dependent manner.","method":"Co-immunoprecipitation, reporter assay, HAT-dead mutant analysis","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — co-IP and HAT-dead functional test, single lab","pmids":["10318892"],"is_preprint":false},{"year":2003,"finding":"P/CAF acetylates the ETS transcription factor ER81 at K116 (and p300 additionally at K33); acetylation enhances ER81 transactivation, DNA binding activity, and in vivo half-life; oncogenic HER2/Neu stimulates p300-mediated ER81 acetylation via the Ras→Raf→MAPK pathway.","method":"In vitro and in vivo acetylation assay, acetylation-deficient mutant analysis, DNA binding assay, protein stability measurement","journal":"Molecular and cellular biology","confidence":"Medium","confidence_rationale":"Tier 1–2 / Moderate — in vitro acetylation with site mutagenesis plus in vivo functional tests; single lab","pmids":["12917345"],"is_preprint":false},{"year":1998,"finding":"NF-Y complex associates with human GCN5 and P/CAF in vivo and possesses HAT activity through these interactions; the NF-YB:YC histone-fold motif is sufficient for stable interaction with GCN5 in vitro; deletion of N- or C-terminal regions of GCN5 disrupts NF-Y interaction.","method":"In vivo co-immunoprecipitation, in vitro interaction assay, deletion mutant analysis, transient transfection reporter assay","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — in vitro and in vivo binding with domain mapping and functional reporter; single lab","pmids":["9430679"],"is_preprint":false},{"year":2002,"finding":"The adenovirus E1B 55-kDa oncoprotein specifically inhibits PCAF-mediated acetylation of p53 at K320 in vivo and in vitro (without affecting histone acetylation or PCAF autoacetylation) by physically binding PCAF and interfering with the PCAF–p53 interaction.","method":"In vitro acetylation assay, co-immunoprecipitation, competition assay, in vivo acetylation measurement","journal":"Molecular and cellular biology","confidence":"Medium","confidence_rationale":"Tier 1–2 / Moderate — in vitro and in vivo enzymatic inhibition with binding competition mechanism; single lab","pmids":["10891493"],"is_preprint":false},{"year":2002,"finding":"MDM2 interacts with PCAF in vitro and in cells and inhibits PCAF-mediated acetylation of p53 at K320 in vitro and in overexpression experiments, repressing PCAF-dependent p53 transcriptional activation without affecting p53 levels.","method":"GST pull-down, co-immunoprecipitation, in vitro acetylation assay, reporter assay, chromatin immunoprecipitation","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — in vitro and in vivo binding plus in vitro enzymatic inhibition; single lab","pmids":["12068014"],"is_preprint":false},{"year":2008,"finding":"PCAF associates with actin and hnRNP U in nuclear extracts via affinity chromatography and protein-protein interaction assays; PCAF-associated HAT activity is released by disruption of the actin–hnRNP U complex; PCAF, actin, and hnRNP U co-occupy promoters and coding regions of pol II genes and associate with nascent ribonucleoprotein complexes, supporting a role for PCAF in pol II transcription elongation.","method":"Affinity chromatography, co-immunoprecipitation, biochemical fractionation, chromatin immunoprecipitation, RNA immunoprecipitation, bromouridine incorporation assay","journal":"Molecular and cellular biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple biochemical methods in single lab; functional elongation link from hnRNP U disruption assay","pmids":["18710935"],"is_preprint":false},{"year":2008,"finding":"PCAF and HDAC4 associate with cardiac sarcomeres (Z-disc and I/A bands) in cardiomyocytes; PCAF acetylates the Z-disc protein MLP (muscle LIM protein); increased acetylation via HDAC inhibition enhances myofilament calcium sensitivity in wild-type but not MLP-knockout mice.","method":"Immunohistochemistry, electron microscopy, co-immunoprecipitation, in vitro acetylation assay, calcium sensitivity measurement, knockout comparison","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct localization, in vitro acetylation, and MLP-KO genetic control; single lab","pmids":["18250163"],"is_preprint":false},{"year":2008,"finding":"PCAF acetylates β-catenin, inhibiting its ubiquitination and increasing its stability; the key ubiquitination sites K19 and K49 of β-catenin are the critical residues for PCAF-induced acetylation and stabilization; PCAF knockdown reduces β-catenin protein level, transcriptional activity, promotes differentiation, and inhibits migration.","method":"Co-immunoprecipitation, in vitro acetylation assay, site-directed mutagenesis, ubiquitination assay, shRNA knockdown, cell migration and differentiation assays","journal":"Molecular biology of the cell","confidence":"High","confidence_rationale":"Tier 1–2 / Moderate — in vitro acetylation, site mutagenesis, ubiquitination competition, and loss-of-function phenotype; multiple orthogonal methods in single lab","pmids":["18987336"],"is_preprint":false},{"year":2013,"finding":"PCAF/KAT2B interacts with GLI1 (downstream effector of Hedgehog signaling) and is required for H3K9 acetylation on Hh target gene promoters; PCAF depletion impairs Hh target gene expression, reduces medulloblastoma/glioblastoma cell proliferation, and reduces tumor-forming potential of neural stem cells in vivo.","method":"Co-immunoprecipitation, siRNA knockdown, ChIP for H3K9ac, proliferation assay, apoptosis assay, in vivo neural stem cell tumor assay","journal":"Cancer research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — co-IP, ChIP, and in vivo assay; single lab, no in vitro reconstitution of direct acetylation","pmids":["23943798"],"is_preprint":false},{"year":2013,"finding":"PCAF acts as a novel E3 ubiquitin ligase for GLI1; in response to genotoxic stress, p53-elevated PCAF promotes GLI1 ubiquitination and proteasome-dependent degradation (requires the ubiquitination domain of PCAF, not a deletion mutant lacking it), thereby inhibiting Hedgehog signaling.","method":"In vitro ubiquitination assay, deletion mutant of PCAF ubiquitination domain, shRNA knockdown of p53/PCAF, GLI1 rescue experiment, in vivo medulloblastoma model","journal":"Cell death and differentiation","confidence":"High","confidence_rationale":"Tier 1–2 / Moderate — in vitro ubiquitination assay, domain-deletion specificity control, genetic rescue, in vivo tumor model; single lab but multiple strong methods","pmids":["24013724"],"is_preprint":false},{"year":2013,"finding":"KAT2B (PCAF) is recruited by dephosphorylated CRTC2 to gluconeogenic gene promoters, where it acetylates H3K9 (H3K9Ac); KAT2B cooperates with WDR5 to stimulate the gluconeogenic program; depletion of KAT2B or WDR5 decreases gluconeogenic gene expression and a KAT2B antagonist lowers blood glucose in insulin-resistant mice.","method":"Mouse knockout/knockdown models, in vitro acetylation assays, ChIP, small-molecule KAT2B inhibitor in vivo","journal":"The Journal of clinical investigation","confidence":"High","confidence_rationale":"Tier 1–2 / Strong — in vitro assay plus in vivo genetic and pharmacological validation across multiple model systems","pmids":["24051374"],"is_preprint":false},{"year":2016,"finding":"KAT2A and KAT2B (PCAF) acetylate PLK4 kinase domain at K45 and K46; K45/K46 acetylation impairs PLK4 kinase activity in vitro (molecular dynamics suggests shift to inactive conformation); the PLK4 K45R/K46R mutant does not cause centrosome overamplification when overexpressed; impairing KAT2A/2B acetyltransferase activity results in excess centrosome numbers in cells.","method":"Shotgun proteomics acetylome, in vitro kinase assay after acetylation, molecular dynamics modelling, mutant overexpression centrosome assay","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 1 / Strong — proteomics substrate identification, in vitro enzymatic assay with mutagenesis, and cellular phenotypic validation; multiple orthogonal methods","pmids":["27796307"],"is_preprint":false},{"year":2014,"finding":"PCAF acetylates PGC-1α at K328 and K450, triggering its proteasomal degradation and suppressing gluconeogenic transcriptional activity; adenoviral PCAF expression in obese mouse liver represses gluconeogenic enzyme activation and improves glucose homeostasis; liver-specific PCAF knockdown increases blood glucose.","method":"In vitro acetylation assay, site-directed mutagenesis, adenoviral overexpression in vivo, liver-specific knockdown, glucose tolerance tests","journal":"Cell reports","confidence":"High","confidence_rationale":"Tier 1–2 / Strong — in vitro enzymatic assay with site mapping, in vivo genetic gain/loss-of-function, metabolic phenotype; multiple methods single lab","pmids":["25497092"],"is_preprint":false},{"year":2015,"finding":"PCAF acetylates EZH2 primarily at K348; K348 acetylation decreases EZH2 phosphorylation at T345 and T487, increases EZH2 stability without disrupting PRC2 formation, and enhances EZH2's capacity to suppress target genes; SIRT1 deacetylates EZH2.","method":"Co-immunoprecipitation, in vitro acetylation assay, site-directed mutagenesis, protein stability assay, PRC2 complex immunoprecipitation","journal":"Nucleic acids research","confidence":"Medium","confidence_rationale":"Tier 1–2 / Moderate — in vitro acetylation with site mapping, mutagenesis, complex analysis; single lab","pmids":["25800736"],"is_preprint":false},{"year":2003,"finding":"PCAF directly interacts with cdk2; PCAF inhibits cyclin/cdk2 activity by two mechanisms: (i) disrupting cyclin–cdk2 interaction and (ii) acetylating cdk2 at K33 (within the ATP-binding pocket), thereby inhibiting cdk2 kinase activity; PCAF overexpression arrests cells at S and G2/M in a cdk2-dependent manner.","method":"Co-immunoprecipitation, in vitro kinase assay, in vitro acetylation with K33 mutagenesis, cell cycle analysis, cdk2 rescue overexpression","journal":"Nucleic acids research","confidence":"Medium","confidence_rationale":"Tier 1–2 / Moderate — in vitro acetylation with site mutagenesis plus cell cycle functional assay; single lab","pmids":["19773423"],"is_preprint":false},{"year":2010,"finding":"During keratinocyte differentiation, PCAF acetylates Rb at sites within its nuclear localization sequence; PCAF HAT activity is required for normal differentiation; acetylation-deficient Rb is mislocalized to the cytoplasm during differentiation, and SIRT1 overexpression or PCAF reduction causes the same Rb mislocalization.","method":"shRNA depletion, HAT-dead PCAF, acetylation-site Rb mutants, subcellular fractionation/immunofluorescence, differentiation assays","journal":"Journal of cell science","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct localization experiment tied to functional consequence, site-specific mutant analysis; single lab","pmids":["20940255"],"is_preprint":false},{"year":2008,"finding":"PCAF is an HIF-1α cofactor that acetylates HIF-1α under hypoxia-mimicking conditions; PCAF-mediated acetylation of p53 at K320 is preferentially reduced under hypoxia compared to K382 acetylation (by p300), redirecting acetylated p53 to p21 promoters while preventing recruitment to pro-apoptotic BID promoter.","method":"Co-immunoprecipitation, chromatin immunoprecipitation, acetylation site-specific analysis under hypoxia","journal":"Oncogene","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — ChIP and co-IP analysis of promoter-specific recruitment; site-specific acetylation under hypoxia; single lab","pmids":["18574470"],"is_preprint":false},{"year":2012,"finding":"PCAF HAT activity is required for stress-induced H3K9 and H3K14 acetylation at the p21 promoter and for p53-dependent p21 transcription in response to multiple stresses (nutlin-3, DNA damage, p14ARF); this role is independent of p53 K320 acetylation; PCAF loss prevents cell cycle arrest.","method":"siRNA knockdown, HAT-dead PCAF mutant, chromatin immunoprecipitation for H3K9ac/H3K14ac, p53 promoter occupancy assay, cell cycle analysis","journal":"Cell cycle (Georgetown, Tex.)","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — ChIP for specific histone marks, HAT-dead mutant, loss-of-function cell cycle phenotype; single lab","pmids":["22713239"],"is_preprint":false},{"year":2017,"finding":"PCAF/GCN5 PCAF-deficient macrophages exhibit markedly reduced cytokine production upon LPS stimulation; chemical inhibition of PCAF/GCN5 bromodomains alone is insufficient to recapitulate this immune phenotype, but PCAF/GCN5 PROTAC-mediated degradation potently modulates inflammatory mediator expression.","method":"PCAF-deficient macrophage functional assay, bromodomain inhibitor comparison, PROTAC-mediated degradation, cytokine expression assay","journal":"ACS chemical biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic KO plus pharmacological PROTAC comparator; demonstrates bromodomain vs. scaffolding/enzymatic activity distinction; single lab","pmids":["30200762"],"is_preprint":false},{"year":2017,"finding":"PCAF acetylates RPA1 at K163; DNA-PK phosphorylates and activates PCAF upon UV damage to promote K163 acetylation; K163 acetylation of RPA1 is critical for accumulation of XPA at damaged DNA and activation of nucleotide excision repair (NER) specifically; HDAC6 and SIRT1 deacetylate RPA1.","method":"In vitro acetylation assay, co-immunoprecipitation, site-directed mutagenesis, NER assay, XPA recruitment to damage sites, HDAC identification","journal":"Cell reports","confidence":"High","confidence_rationale":"Tier 1–2 / Strong — in vitro acetylation with site mapping, upstream kinase (DNA-PK) identified, eraser (HDAC6/SIRT1) identified, pathway-specific functional assay (NER vs other repair); multiple orthogonal methods","pmids":["28854354"],"is_preprint":false},{"year":2020,"finding":"PCAF is a fork-associated protein at stalled replication forks; PCAF acetylates H4K8 at stalled forks, recruiting MRE11 and EXO1 (via an H4K8ac-binding domain) to promote fork degradation in BRCA-deficient cells; ATR phosphorylates PCAF at S264 to limit its fork association and activity; low PCAF levels stabilize stalled forks and cause PARPi resistance in BRCA-deficient cells.","method":"Chromatin fractionation at forks, in vitro H4K8 acetylation assay, S264 phospho-site mapping, MRE11/EXO1 H4K8ac binding domain analysis, PARPi resistance assay, ATR inhibition","journal":"Molecular cell","confidence":"High","confidence_rationale":"Tier 1–2 / Strong — in vitro acetylation, binding domain mapping, upstream regulator (ATR) identified, functional fork stability/PARPi resistance readout; rigorous multi-method single lab","pmids":["32966758"],"is_preprint":false},{"year":2009,"finding":"hSIRT1 deacetylates PCAF in vitro and modulates PCAF acetylation in vivo; hSIRT1 represses E2F1-dependent p73 promoter activity by forming a hSIRT1–PCAF–E2F1 complex on the P1p73 promoter; upon apoptotic DNA damage, decreased nuclear NAD+ inactivates hSIRT1's deacetylase activity (without disrupting SIRT1–PCAF interaction), releasing PCAF to form active PCAF/E2F1 complexes on the P1p73 promoter.","method":"In vitro deacetylation assay, co-immunoprecipitation, chromatin immunoprecipitation, NAD+ manipulation, reporter assay","journal":"Molecular and cellular biology","confidence":"Medium","confidence_rationale":"Tier 1–2 / Moderate — in vitro deacetylation plus ChIP and co-IP; single lab but mechanistic detail of NAD+ regulation tested","pmids":["19188449"],"is_preprint":false},{"year":2010,"finding":"PTH treatment increases PCAF acetylation at the MMP-13 promoter in a p300-dependent manner; p300-dependent PCAF acetylation and mutual p300–PCAF promoter recruitment is required for PTH-induced MMP-13 transcription; HAT activities of both PCAF and p300 are additively required.","method":"ChIP, siRNA knockdown of PCAF/p300/Runx2, reporter assay with HAT-dead mutants","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — ChIP, siRNA knockdown, and HAT-dead mutant analyses; single lab","pmids":["20870727"],"is_preprint":false},{"year":2013,"finding":"PCAF directly acetylates cytoplasmic GLI1 at K518, preventing its nuclear translocation and promoter occupancy, suppressing Hedgehog signaling in hepatocellular carcinoma; PCAF-mediated GLI1 acetylation reduces BCL2 expression and upregulates BAX.","method":"In vitro acetylation assay, site-directed mutagenesis, subcellular fractionation, ChIP, in vivo xenograft model","journal":"Cell death & disease","confidence":"Medium","confidence_rationale":"Tier 1–2 / Moderate — in vitro acetylation with site mapping, localization assay, and in vivo tumor model; single lab","pmids":["25855960"],"is_preprint":false},{"year":2008,"finding":"GCN5L (KAT2B) stably associates with Mediator containing the cdk8 subcomplex (T/G-Mediator) together with TRRAP; cdk8 phosphorylates H3 serine-10, which then stimulates H3K14 acetylation by GCN5L within the complex, producing tandem H3 phosphoacetylation that correlates with transcriptional activation.","method":"Reconstituted human transcription system, co-immunoprecipitation, in vitro histone modification assay, cdk8 knockdown, ChIP","journal":"The EMBO journal","confidence":"High","confidence_rationale":"Tier 1 / Strong — reconstituted in vitro transcription/modification system plus cellular ChIP validation; rigorous biochemical dissection","pmids":["18418385"],"is_preprint":false},{"year":2014,"finding":"PCAF (Kat2b) and Gcn5 negatively regulate IFN-β production through a HAT-independent, non-transcriptional mechanism by inhibiting the innate immune kinase TBK1 in the cytoplasm; Gcn5/PCAF-mediated H3K9ac is dispensable for IFNB expression and the vast majority of active genes in fibroblasts.","method":"HAT-dead mutant analysis, cytoplasmic TBK1 inhibition assay, genetic knockout of Gcn5/PCAF, IFN-β production assay","journal":"EMBO reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — HAT-dead mutant dissects HAT-independent function; cytoplasmic TBK1 inhibition demonstrated; single lab","pmids":["25269644"],"is_preprint":false},{"year":2013,"finding":"PCAF acetylates HOXA10 at K338 and K339, inhibiting HOXA10-mediated ITGB3 (β3-integrin) transcription and thereby impairing endometrial receptivity and embryo adhesion.","method":"Co-immunoprecipitation, in vitro acetylation assay with site mapping, luciferase reporter assay, ChIP, BeWo spheroid attachment assay, PCAF overexpression/knockdown","journal":"The Journal of clinical endocrinology and metabolism","confidence":"Medium","confidence_rationale":"Tier 1–2 / Moderate — in vitro acetylation with site mapping, ChIP, functional adhesion assay; single lab","pmids":["24037888"],"is_preprint":false},{"year":2012,"finding":"PCAF directly interacts with p27Kip1 (via aa 91–120 of p27; PCAF catalytic domain required) and acetylates p27 at K100; PCAF overexpression induces proteasomal degradation of p27 (Skp2-independent); K100R mutant p27 is resistant to PCAF-induced degradation and remains stable through the cell cycle.","method":"Co-immunoprecipitation, in vitro acetylation assay, K100R mutagenesis, protein half-life measurement, proteasome inhibitor assay, ubiquitylation assay","journal":"Nucleic acids research","confidence":"Medium","confidence_rationale":"Tier 1–2 / Moderate — in vitro acetylation with site mutagenesis, proteasomal pathway confirmed; single lab","pmids":["22547391"],"is_preprint":false},{"year":2020,"finding":"PCAF-dependent acetylation of ISX at K69 promotes ISX interaction with BRD4 (acetylated at K332) and nuclear translocation of the ISX–BRD4 complex; in the nucleus, the complex binds EMT gene promoters with H3K9/K14/K18 acetylation, activating EMT transcription and cancer metastasis.","method":"Co-immunoprecipitation, site-directed mutagenesis, subcellular fractionation, ChIP, histone acetylation analysis","journal":"EMBO reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — co-IP, mutagenesis, ChIP, and nuclear localization assays; single lab","pmids":["31908141"],"is_preprint":false},{"year":2020,"finding":"SIRT7 directly interacts with PCAF and deacetylates PCAF at K720 upon glucose deprivation; deacetylated PCAF binds MDM2 more strongly, promoting MDM2 ubiquitination/degradation, elevating p53, and inducing p21/cell-cycle arrest.","method":"Co-immunoprecipitation, in vitro deacetylation assay, K720 site mapping, MDM2 ubiquitination assay, cell cycle analysis","journal":"Oncogene","confidence":"Medium","confidence_rationale":"Tier 1–2 / Moderate — in vitro deacetylation assay, site-specific mutagenesis, downstream ubiquitination assay; single lab","pmids":["32404984"],"is_preprint":false},{"year":2013,"finding":"PCAF interacts with GLI1 and ubiquitinates it (E3 ubiquitin ligase activity), inhibiting HCC cell metastasis and EMT; PCAF-mediated GLI1 targeting suppresses Gli1-driven EMT in hepatocellular carcinoma.","method":"Co-immunoprecipitation, in vitro ubiquitination assay, siRNA knockdown, migration/invasion assay","journal":"Cancer letters","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — co-IP plus in vitro ubiquitination plus cellular functional assay; single lab","pmids":["26945969"],"is_preprint":false},{"year":2017,"finding":"PCAF acetylates MKL1 in response to pro-inflammatory stimuli (TNF-α, LPS); acetylation promotes MKL1 nuclear enrichment, enhances MKL1–NF-κB interaction, and stabilizes MKL1 binding to NF-κB target promoters, activating pro-inflammatory transcription.","method":"Co-immunoprecipitation, in vivo acetylation analysis, MKL1 lysine mutant functional assay, nuclear fractionation, ChIP","journal":"Biochimica et biophysica acta. Gene regulatory mechanisms","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — co-IP, acetylation mutant, ChIP, and nuclear localization analysis; single lab","pmids":["28571745"],"is_preprint":false},{"year":2013,"finding":"PCAF regulates the EB1–TIP150 interaction at kinetochore microtubule plus ends by acetylating EB1; persistent EB1 acetylation by PCAF perturbs the EB1–TIP150 interaction, leading to metaphase alignment defects, spindle checkpoint activation, and chromosome aneuploidy.","method":"siRNA knockdown, co-immunoprecipitation, acetylation assay, live cell imaging of chromosome alignment, spindle checkpoint assay","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — co-IP, acetylation assay, and cellular kinetochore phenotype; single lab","pmids":["23595990"],"is_preprint":false},{"year":2018,"finding":"PCAF (and GCN5) acetylate influenza A virus nucleoprotein (NP) in vitro; PCAF acetylates NP at Lys-31 while GCN5 targets Lys-90; PCAF silencing increases viral polymerase activity, indicating that PCAF-mediated NP acetylation at K31 negatively regulates influenza replication.","method":"In vitro acetyltransferase assay, LC-MS site identification, RNAi silencing, viral polymerase activity assay","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 1 / Moderate — in vitro enzymatic assay with MS site mapping plus RNAi functional test; single lab","pmids":["29555684"],"is_preprint":false},{"year":2003,"finding":"PCAF binds p73; the N-terminal transactivation domain and OD of p73 and the HAT domain of PCAF are required for interaction; PCAF HAT activity is required for stimulating p73-mediated transactivation of p21 and induction of apoptosis.","method":"Co-immunoprecipitation, domain mapping, reporter assay, PCAF-specific siRNA, colony formation assay","journal":"Oncogene","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — co-IP domain mapping, HAT-dead mutant, and siRNA functional test; single lab","pmids":["14614455"],"is_preprint":false},{"year":2010,"finding":"PCAF and CBP/p300 are repressed by inhibitory (myelin, CSPG) substrates in neurons; HDAC inhibition restores PCAF/CBP/p300 expression; PCAF and CBP/p300 acetylate histone H3 at K9–14 and p53, initiating a pro-neuronal outgrowth transcriptional program that promotes axon growth and counteracts growth cone collapse.","method":"Gene silencing, gain-of-function, chromatin acetylation analysis, neurite outgrowth quantification","journal":"Cell death and differentiation","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — loss/gain-of-function with acetylation readout and outgrowth phenotype; single lab","pmids":["20094059"],"is_preprint":false},{"year":2014,"finding":"Gcn5 and PCAF double knockout blocks PPARγ expression (preventing adipocyte differentiation) and is essential for Prdm16 expression (required for brown adipogenesis); Gcn5/PCAF facilitate PPARγ RNA pol II recruitment and Prdm16 transcript elongation.","method":"Double-knockout cell lines, PPARγ rescue expression, ChIP for pol II, nascent RNA analysis","journal":"Molecular and cellular biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — double-KO genetic model with ChIP and rescue experiments; single lab","pmids":["25071153"],"is_preprint":false},{"year":2010,"finding":"HIPK2 cooperates with PCAF to induce PCAF-mediated p53 acetylation after nonapoptotic DNA damage; HIPK2 depletion abolishes PCAF-dependent p53 acetylation and reduces p53 binding to the p21Waf1 promoter, inhibiting p21 transactivation and allowing cell proliferation.","method":"RNAi knockdown of HIPK2, ChIP, acetylation analysis, cell cycle assay","journal":"Oncogene","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — epistasis via RNAi knockdown, ChIP, and acetylation site analysis; single lab","pmids":["15897882"],"is_preprint":false}],"current_model":"KAT2B (PCAF) is a lysine acetyltransferase (GNAT superfamily) that operates via an ordered Bi-Bi mechanism with acetyl-CoA binding first, targeting histone H3K9/K14 and a broad range of non-histone substrates including p53 (K320), β-catenin, PLK4 (K45/K46), RPA1 (K163), PGC-1α, PTEN, EZH2, cdk2 (K33), GLI1 (K518), MKL1, Rb, and others; it also possesses a distinct intrinsic E3 ubiquitin ligase activity targeting Hdm2 and GLI1; its nuclear localization is regulated by autoacetylation of its NLS (deacetylated by HDAC3/SIRT1 causing cytoplasmic accumulation); its acetyltransferase activity is activated by auto-acetylation and p300-mediated acetylation, inhibited by viral oncoproteins (E1A, E1B-55K), MDM2, and DEK, and regulated by ATR phosphorylation at S264 at stalled replication forks; PCAF participates in large multiprotein complexes (STAGA/TFTC/ATAC) and cooperates with p300/CBP as a transcriptional co-activator for nuclear receptors, MyoD, Notch/RBP-J, Smads, p73, GLI1, and other factors, while also functioning as a HAT-independent cytoplasmic inhibitor of TBK1 to negatively regulate innate IFN-β production."},"narrative":{"mechanistic_narrative":"KAT2B (PCAF) is a GNAT-family lysine acetyltransferase that functions as a transcriptional co-activator and broad-spectrum protein-modifying enzyme, coupling chromatin acetylation to the control of cell differentiation, cell-cycle progression, genome maintenance, and metabolism [PMID:9742083, PMID:11009610, PMID:9659901]. Mechanistically it catalyzes acetyl transfer through a fully ordered Bi-Bi mechanism in which acetyl-CoA binds first and acetyl transfer to histone H3 Lys-14 is rate-determining, with Glu-570 acting as the proposed general base; its extended N-terminal domain (relative to yeast Gcn5p) enables acetylation of nucleosomal as well as free histones [PMID:11009610, PMID:9742083]. On chromatin, KAT2B deposits H3K9/H3K14 acetylation cooperatively with p300/CBP and within larger machines, including a cdk8-containing Mediator complex where H3 Ser-10 phosphorylation stimulates KAT2B-mediated H3K14 acetylation to produce activating tandem phosphoacetylation [PMID:18418385, PMID:9742083]. Through direct interactions it serves as a co-activator for diverse transcription factors and signaling effectors—MyoD-driven myogenesis and p21 induction, nuclear receptors, TGF-β/Smad3, Notch/RBP-J, p73, and GLI1—frequently requiring its intrinsic HAT activity [PMID:9659901, PMID:9620851, PMID:11058129, PMID:10747963, PMID:14614455, PMID:23943798]. Beyond histones, KAT2B acetylates a wide range of non-histone substrates to alter their activity, stability, or localization: p53 at K320 to enhance DNA binding after damage [PMID:9891054], PTEN at K125/K128 to dampen its lipid-phosphatase activity and sustain PI3K/AKT signaling [PMID:16829519], β-catenin at ubiquitination sites K19/K49 to block its degradation [PMID:18987336], EZH2 at K348 to stabilize it [PMID:25800736], cdk2 at K33 and p27 at K100 to restrain cell-cycle kinases [PMID:19773423, PMID:22547391], PLK4 at K45/K46 to limit centrosome amplification [PMID:27796307], PGC-1α to trigger its degradation and suppress gluconeogenesis [PMID:25497092], and RPA1 at K163 to drive nucleotide excision repair [PMID:28854354]. KAT2B also carries a mechanistically distinct intrinsic E3 ubiquitin ligase activity that ubiquitinates Hdm2 (stabilizing p53) and GLI1 (terminating Hedgehog signaling) [PMID:17293853, PMID:24013724]. At the genome it acts at stalled replication forks, where it acetylates H4K8 to recruit MRE11/EXO1 and promote fork degradation, an activity restrained by ATR phosphorylation at S264 [PMID:32966758]. Its own nuclear localization is governed by autoacetylation of a C-terminal NLS, which is reversed by HDAC3/SIRT1 to drive cytoplasmic accumulation [PMID:19015268, PMID:12888487], and a cytoplasmic, HAT-independent pool inhibits the kinase TBK1 to negatively regulate IFN-β production [PMID:25269644]. KAT2B is functionally redundant with GCN5, which is upregulated in PCAF-null mice to compensate [PMID:11027331].","teleology":[{"year":1998,"claim":"Established that human PCAF/GCN5 differ from yeast Gcn5p by acetylating nucleosomal substrates, defining KAT2B as a bona fide chromatin-modifying enzyme that partners with CBP/p300.","evidence":"In vitro HAT assays on free versus nucleosomal histones with comparative domain analysis","pmids":["9742083"],"confidence":"High","gaps":["Did not resolve which complexes target it to chromatin in vivo","Substrate site specificity on nucleosomes not fully mapped"]},{"year":2000,"claim":"Defined the catalytic mechanism, showing KAT2B uses an ordered Bi-Bi mechanism with acetyl-CoA binding first and acetyl transfer as the rate-limiting chemical step.","evidence":"Bi-substrate kinetics, product inhibition, equilibrium dialysis, and pre-steady-state quench-flow on H3 peptide","pmids":["11009610"],"confidence":"High","gaps":["Kinetics established on peptide, not full nucleosomes","General-base role of Glu-570 inferred, not structurally proven in this study"]},{"year":1997,"claim":"Showed KAT2B HAT activity is specifically required for terminal differentiation, linking its enzymatic function to p21 induction and cell-cycle exit in myogenesis.","evidence":"Anti-PCAF antibody microinjection, HAT-dead mutant, and reporter assays in muscle differentiation","pmids":["9659901"],"confidence":"High","gaps":["Direct substrates driving p21 induction not pinned to histone vs non-histone","Did not separate PCAF from GCN5 contribution"]},{"year":1999,"claim":"Identified the first non-histone substrate, p53 at K320, showing acetylation enhances p53 DNA binding and is induced by DNA damage—extending KAT2B function beyond chromatin.","evidence":"In vitro acetyltransferase assay with site-specific antibodies and in vivo detection after genotoxic stress","pmids":["9891054"],"confidence":"High","gaps":["Erasers of K320 not identified here","In vivo functional consequence for specific target genes not resolved"]},{"year":1999,"claim":"Demonstrated that viral and cellular antagonists directly inhibit KAT2B, establishing it as a regulated node; E1A, E1B-55K, and MDM2 bind PCAF and block its acetylation of p53.","evidence":"Direct binding and in vitro/in vivo HAT inhibition assays for E1A, E1B-55K, and MDM2","pmids":["10025405","10891493","12068014"],"confidence":"High","gaps":["Structural basis of inhibition not fully resolved","Whether inhibition is global or substrate-selective varies by antagonist"]},{"year":2000,"claim":"Genetically established functional redundancy between KAT2B and GCN5, explaining the viability of PCAF-null animals.","evidence":"PCAF-knockout mouse with Western quantification of compensatory GCN5 upregulation","pmids":["11027331"],"confidence":"High","gaps":["Did not identify non-redundant KAT2B-specific functions in vivo","Tissue-specific requirements not dissected"]},{"year":2003,"claim":"Showed KAT2B activity and localization are self-regulated by autoacetylation, with p300 also acetylating it and autoacetylation boosting HAT activity.","evidence":"In vitro and in vivo acetylation assays with NLS-lysine mutagenesis","pmids":["12888487"],"confidence":"Medium","gaps":["Single lab without independent replication","Quantitative contribution of inter- vs intramolecular autoacetylation unclear"]},{"year":2008,"claim":"Connected autoacetylation to subcellular control, showing NLS acetylation drives nuclear retention while HDAC3/SIRT1 deacetylation causes cytoplasmic accumulation.","evidence":"Subcellular fractionation, imaging, HAT-dead mutants, and HDAC manipulation","pmids":["19015268"],"confidence":"Medium","gaps":["Signals triggering deacetylation-driven export not defined","Single lab"]},{"year":2007,"claim":"Revealed a second, mechanistically distinct enzymatic activity: an intrinsic E3 ubiquitin ligase that ubiquitinates Hdm2 to stabilize p53.","evidence":"In vitro ubiquitination assay plus knockdown phenotype with domain deletion","pmids":["17293853"],"confidence":"High","gaps":["Catalytic ubiquitin-ligase residues not fully mapped","Relationship between HAT and E3 domains structurally unresolved"]},{"year":2013,"claim":"Extended the dual-enzyme model to Hedgehog signaling, showing KAT2B both supports GLI1-dependent H3K9ac on target promoters and ubiquitinates/acetylates GLI1 to terminate or restrain the pathway.","evidence":"Co-IP, ChIP, in vitro ubiquitination/acetylation, site mutagenesis, and in vivo tumor models","pmids":["23943798","24013724","25855960","26945969"],"confidence":"Medium","gaps":["Context determining co-activator vs degradative role not resolved","Direct GLI1 acetylation not reconstituted in every report"]},{"year":2016,"claim":"Broadened the non-histone substrate repertoire to cell-cycle and centrosome control, identifying acetylation of cdk2 (K33), p27 (K100), and PLK4 (K45/K46) as inhibitory modifications.","evidence":"Acetylome proteomics, in vitro acetylation with site mutagenesis, kinase assays, and centrosome/cell-cycle phenotypes","pmids":["27796307","22547391","19773423"],"confidence":"High","gaps":["Endogenous stoichiometry of these acetylations unclear","Erasers not identified for all sites"]},{"year":2014,"claim":"Established KAT2B as a metabolic regulator of hepatic gluconeogenesis through both histone and non-histone routes, with pharmacological tractability for glycemic control.","evidence":"In vitro acetylation, ChIP, liver-specific knockdown/overexpression, and small-molecule inhibitor in metabolic mouse models","pmids":["24051374","25497092"],"confidence":"High","gaps":["Reconciliation of gluconeogenesis-promoting (H3K9ac/CRTC2) and -suppressing (PGC-1α degradation) roles not fully integrated","Tissue selectivity of inhibitor not detailed"]},{"year":2017,"claim":"Placed KAT2B in the DNA-damage response, showing DNA-PK-activated KAT2B acetylates RPA1 at K163 to promote XPA recruitment and nucleotide excision repair.","evidence":"In vitro acetylation with site mapping, upstream kinase and eraser identification, and pathway-specific NER assays","pmids":["28854354"],"confidence":"High","gaps":["Selectivity for NER over other repair pathways mechanism not fully explained","Single lab"]},{"year":2020,"claim":"Defined a replication-fork function in which KAT2B acetylates H4K8 to recruit nucleases for fork degradation, with ATR phosphorylation at S264 acting as a brake relevant to PARPi resistance.","evidence":"Chromatin fractionation, in vitro H4K8 acetylation, phospho-site mapping, H4K8ac-binding domain analysis, and PARPi resistance assays","pmids":["32966758"],"confidence":"High","gaps":["How fork-localized KAT2B is initially recruited not fully defined","Relevance across BRCA-proficient contexts not established"]},{"year":2014,"claim":"Uncovered a HAT-independent cytoplasmic function, with KAT2B and GCN5 inhibiting TBK1 to negatively regulate IFN-β, decoupling an immune role from histone acetylation.","evidence":"HAT-dead mutants, genetic knockout, cytoplasmic TBK1 inhibition, and IFN-β assays","pmids":["25269644"],"confidence":"Medium","gaps":["Direct biochemical mode of TBK1 inhibition not resolved","Single lab"]},{"year":null,"claim":"How KAT2B's two catalytic activities (acetyltransferase and E3 ubiquitin ligase), its autoacetylation-controlled localization, and its many context-dependent substrates are coordinated and selected in a given cell remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structural model integrating HAT and ubiquitin-ligase activities","Substrate-selection rules in vivo undefined","Functional separation from GCN5 across tissues incomplete"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0016740","term_label":"transferase activity","supporting_discovery_ids":[7,6,0,10,24,28,36,37]},{"term_id":"GO:0140096","term_label":"catalytic activity, acting on a protein","supporting_discovery_ids":[0,10,24,28,31,44,36]},{"term_id":"GO:0016874","term_label":"ligase activity","supporting_discovery_ids":[11,26,47]},{"term_id":"GO:0140110","term_label":"transcription regulator activity","supporting_discovery_ids":[1,2,13,41]},{"term_id":"GO:0042393","term_label":"histone binding","supporting_discovery_ids":[6,41]}],"localization":[{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[9,8,41]},{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[9,42]},{"term_id":"GO:0000228","term_label":"nuclear chromosome","supporting_discovery_ids":[37,34]}],"pathway":[{"term_id":"R-HSA-74160","term_label":"Gene expression (Transcription)","supporting_discovery_ids":[1,2,13,41,6]},{"term_id":"R-HSA-1640170","term_label":"Cell Cycle","supporting_discovery_ids":[31,44,28,34]},{"term_id":"R-HSA-73894","term_label":"DNA Repair","supporting_discovery_ids":[36,37]},{"term_id":"R-HSA-1430728","term_label":"Metabolism","supporting_discovery_ids":[27,29]},{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[25,26,10,24]},{"term_id":"R-HSA-168256","term_label":"Immune System","supporting_discovery_ids":[42,48]},{"term_id":"R-HSA-1266738","term_label":"Developmental Biology","supporting_discovery_ids":[1,53,52]}],"complexes":["STAGA/TFTC/ATAC","cdk8-Mediator (T/G-Mediator)","PRC2 (associated via EZH2)"],"partners":["EP300","GCN5","TP53","MDM2","GLI1","MYOD1","SMAD3","SIRT1"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q92831","full_name":"Histone acetyltransferase KAT2B","aliases":["Histone acetyltransferase PCAF","Histone acetylase PCAF","Lysine acetyltransferase 2B","P300/CBP-associated factor","P/CAF","Spermidine acetyltransferase KAT2B"],"length_aa":832,"mass_kda":93.0,"function":"Functions as a histone acetyltransferase (HAT) to promote transcriptional activation (PubMed:8945521). Has significant histone acetyltransferase activity with core histones (H3 and H4), and also with nucleosome core particles (PubMed:8945521). Has a a strong preference for acetylation of H3 at 'Lys-9' (H3K9ac) (PubMed:21131905). Also acetylates non-histone proteins, such as ACLY, MAPRE1/EB1, PLK4, RRP9/U3-55K and TBX5 (PubMed:10675335, PubMed:23001180, PubMed:23932781, PubMed:26867678, PubMed:27796307, PubMed:29174768, PubMed:9707565). Inhibits cell-cycle progression and counteracts the mitogenic activity of the adenoviral oncoprotein E1A (PubMed:8684459). Acts as a circadian transcriptional coactivator which enhances the activity of the circadian transcriptional activators: NPAS2-BMAL1 and CLOCK-BMAL1 heterodimers (PubMed:14645221). Involved in heart and limb development by mediating acetylation of TBX5, acetylation regulating nucleocytoplasmic shuttling of TBX5 (PubMed:29174768). Acts as a negative regulator of centrosome amplification by mediating acetylation of PLK4 (PubMed:27796307). Acetylates RRP9/U3-55K, a core subunit of the U3 snoRNP complex, impairing pre-rRNA processing (PubMed:26867678). Acetylates MAPRE1/EB1, promoting dynamic kinetochore-microtubule interactions in early mitosis (PubMed:23001180). Also acetylates spermidine (PubMed:27389534) (Microbial infection) In case of HIV-1 infection, it is recruited by the viral protein Tat. Regulates Tat's transactivating activity and may help inducing chromatin remodeling of proviral genes","subcellular_location":"Nucleus; Cytoplasm, cytoskeleton, microtubule organizing center, centrosome; Cytoplasm","url":"https://www.uniprot.org/uniprotkb/Q92831/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/KAT2B","classification":"Not Classified","n_dependent_lines":4,"n_total_lines":1208,"dependency_fraction":0.0033112582781456954},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"TRRAP","stoichiometry":4.0},{"gene":"SF3B3","stoichiometry":0.2},{"gene":"SF3B5","stoichiometry":0.2},{"gene":"TAF12","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/KAT2B","total_profiled":1310},"omim":[{"mim_id":"618788","title":"COILED-COIL DOMAIN-CONTAINING PROTEIN 134; CCDC134","url":"https://www.omim.org/entry/618788"},{"mim_id":"617501","title":"LYSINE ACETYLTRANSFERASE 14; KAT14","url":"https://www.omim.org/entry/617501"},{"mim_id":"617008","title":"CEREBRAL PALSY, SPASTIC QUADRIPLEGIC, 3; CPSQ3","url":"https://www.omim.org/entry/617008"},{"mim_id":"613374","title":"COILED-COIL DOMAIN-CONTAINING PROTEIN 101; CCDC101","url":"https://www.omim.org/entry/613374"},{"mim_id":"613373","title":"YEATS DOMAIN-CONTAINING PROTEIN 2; YEATS2","url":"https://www.omim.org/entry/613373"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Enhanced","locations":[{"location":"Nucleoplasm","reliability":"Enhanced"},{"location":"Cytosol","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/KAT2B"},"hgnc":{"alias_symbol":["P/CAF","GCN5","GCN5L"],"prev_symbol":["PCAF"]},"alphafold":{"accession":"Q92831","domains":[{"cath_id":"-","chopping":"69-118_130-201","consensus_level":"high","plddt":86.0011,"start":69,"end":201},{"cath_id":"-","chopping":"222-366","consensus_level":"medium","plddt":88.8792,"start":222,"end":366},{"cath_id":"3.40.630.30","chopping":"483-662","consensus_level":"high","plddt":92.8583,"start":483,"end":662},{"cath_id":"1.20.920.10","chopping":"726-828","consensus_level":"high","plddt":92.939,"start":726,"end":828}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q92831","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q92831-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q92831-F1-predicted_aligned_error_v6.png","plddt_mean":76.12},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=KAT2B","jax_strain_url":"https://www.jax.org/strain/search?query=KAT2B"},"sequence":{"accession":"Q92831","fasta_url":"https://rest.uniprot.org/uniprotkb/Q92831.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q92831/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q92831"}},"corpus_meta":[{"pmid":"21131905","id":"PMC_21131905","title":"Distinct roles of GCN5/PCAF-mediated H3K9ac and CBP/p300-mediated H3K18/27ac in nuclear receptor transactivation.","date":"2010","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/21131905","citation_count":673,"is_preprint":false},{"pmid":"9891054","id":"PMC_9891054","title":"p53 sites acetylated in vitro by PCAF and p300 are acetylated in vivo in response to DNA damage.","date":"1999","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/9891054","citation_count":658,"is_preprint":false},{"pmid":"9659901","id":"PMC_9659901","title":"Differential roles of p300 and PCAF acetyltransferases in muscle differentiation.","date":"1997","source":"Molecular cell","url":"https://pubmed.ncbi.nlm.nih.gov/9659901","citation_count":372,"is_preprint":false},{"pmid":"9620851","id":"PMC_9620851","title":"The histone acetylase PCAF is a nuclear receptor coactivator.","date":"1998","source":"Genes & development","url":"https://pubmed.ncbi.nlm.nih.gov/9620851","citation_count":327,"is_preprint":false},{"pmid":"17694077","id":"PMC_17694077","title":"Distinct GCN5/PCAF-containing complexes function as co-activators and are involved in transcription factor and global histone acetylation.","date":"2007","source":"Oncogene","url":"https://pubmed.ncbi.nlm.nih.gov/17694077","citation_count":317,"is_preprint":false},{"pmid":"10025405","id":"PMC_10025405","title":"A viral mechanism for inhibition of p300 and PCAF acetyltransferase activity.","date":"1999","source":"Cell","url":"https://pubmed.ncbi.nlm.nih.gov/10025405","citation_count":297,"is_preprint":false},{"pmid":"9733796","id":"PMC_9733796","title":"Activation of integrated provirus requires histone acetyltransferase. p300 and P/CAF are coactivators for HIV-1 Tat.","date":"1998","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/9733796","citation_count":268,"is_preprint":false},{"pmid":"12391150","id":"PMC_12391150","title":"p300 and PCAF act cooperatively to mediate transcriptional activation from chromatin templates by notch intracellular domains in vitro.","date":"2002","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/12391150","citation_count":217,"is_preprint":false},{"pmid":"16829519","id":"PMC_16829519","title":"PCAF modulates PTEN activity.","date":"2006","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/16829519","citation_count":190,"is_preprint":false},{"pmid":"11027331","id":"PMC_11027331","title":"Distinct but overlapping roles of histone acetylase PCAF and of the closely related PCAF-B/GCN5 in mouse embryogenesis.","date":"2000","source":"Proceedings of the National Academy of Sciences of the United States of 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Regulatory, integrative and comparative physiology","url":"https://pubmed.ncbi.nlm.nih.gov/24944246","citation_count":25,"is_preprint":false},{"pmid":"33894414","id":"PMC_33894414","title":"In-vitro acetylation of SARS-CoV and SARS-CoV-2 nucleocapsid proteins by human PCAF and GCN5.","date":"2021","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/33894414","citation_count":22,"is_preprint":false},{"pmid":"28678170","id":"PMC_28678170","title":"Differential Effects of Histone Acetyltransferase GCN5 or PCAF Knockdown on Urothelial Carcinoma Cells.","date":"2017","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/28678170","citation_count":22,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":49269,"output_tokens":13116,"usd":0.172273,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":24875,"output_tokens":5432,"usd":0.130087,"stage2_stop_reason":"end_turn"},"total_usd":0.30236,"stage1_batch_id":"msgbatch_01DUPACZi7AAWwuZiUjseQF4","stage2_batch_id":"msgbatch_018yt7chE3f48PEFtDwtj6AE","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 1999,\n      \"finding\": \"PCAF acetylates p53 in vitro at lysine K320, a residue distinct from that acetylated by p300, and this acetylation increases p53's ability to bind its cognate DNA site. Acetylation at this site is detected in vivo and increases in response to DNA-damaging agents.\",\n      \"method\": \"In vitro acetyltransferase assay, site-specific acetylation antibodies, in vivo detection after DNA damage\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — in vitro enzymatic assay with site identification, validated in vivo with specific antibodies, independently replicated across multiple studies\",\n      \"pmids\": [\"9891054\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1997,\n      \"finding\": \"PCAF directly interacts with MyoD and forms a multimeric complex with p300/CBP on promoter elements to drive myogenic differentiation; the histone acetyltransferase activity of PCAF (but not p300) is required for p21 expression and terminal cell-cycle arrest during myogenesis.\",\n      \"method\": \"Anti-PCAF antibody microinjection, exogenous expression, reporter assays, HAT-dead mutant analysis\",\n      \"journal\": \"Molecular cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — loss-of-function (antibody microinjection), gain-of-function, and HAT mutant experiments all converge on same conclusion\",\n      \"pmids\": [\"9659901\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1998,\n      \"finding\": \"PCAF directly associates with the DNA-binding domain of nuclear receptors (RXR/RAR heterodimer) in a ligand-dependent manner and independently of p300/CBP, defining a novel cofactor interaction surface on nuclear receptors.\",\n      \"method\": \"Ligand-dependent recruitment from mammalian cell extracts, in vitro direct binding assay, transcription reporter assays\",\n      \"journal\": \"Genes & development\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct binding shown in vitro and in cell extracts with ligand-dependence confirmed; single lab\",\n      \"pmids\": [\"9620851\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1999,\n      \"finding\": \"Adenoviral E1A directly binds PCAF independently of CBP and inhibits PCAF HAT activity in vitro, blocking nucleosomal histone modification by the PCAF complex and p53 acetylation.\",\n      \"method\": \"In vitro HAT assay, direct binding assay, in vivo transcription assays\",\n      \"journal\": \"Cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — direct in vitro enzymatic inhibition demonstrated, replicated across labs (also PMID:9687513)\",\n      \"pmids\": [\"10025405\", \"9687513\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1998,\n      \"finding\": \"PCAF forms a ternary complex with p300 and HIV-1 Tat in cells, and the HAT activity of PCAF (but not p300) is specifically required for Tat transactivation of integrated (but not unintegrated) HIV-1 LTR.\",\n      \"method\": \"Co-immunoprecipitation (ternary complex), dominant-negative HAT mutant transfection, integrated vs. unintegrated LTR reporter assays\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal co-IP plus HAT-dead mutant dissection of integrated vs. episomal LTR, mechanistically rigorous\",\n      \"pmids\": [\"9733796\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2000,\n      \"finding\": \"Mouse Notch1 intracellular region (RAMIC) directly interacts with mouse PCAF (and GCN5) through its ankyrin repeats and transactivation domain, recruiting PCAF to RBP-J and facilitating RBP-J-mediated transactivation; the N-terminal regions of PCAF/GCN5 are required for this interaction.\",\n      \"method\": \"Co-immunoprecipitation, domain mapping, transactivation reporter assays, E1A and Twist inhibition\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — co-IP domain mapping and functional reporter assays in single lab\",\n      \"pmids\": [\"10747963\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1998,\n      \"finding\": \"Human GCN5 and P/CAF have extended homologous amino-terminal domains enabling acetylation of nucleosomal substrates (not only free histones), unlike the shorter yeast Gcn5p; both interact with CBP/p300 and display similar substrate specificities for histone H3.\",\n      \"method\": \"In vitro HAT assay with nucleosomal and free histone substrates, protein interaction assays, immunodetection\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — reconstituted in vitro HAT assay with nucleosomal substrates, comparative domain analysis\",\n      \"pmids\": [\"9742083\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2000,\n      \"finding\": \"Kinetic mechanism of human P/CAF follows a fully ordered Bi-Bi mechanism: acetyl-CoA binds first to free enzyme (Kd = 0.64 µM), then histone H3 peptide binds; chemical catalysis (acetyl transfer to Lys-14 of H3) is rate-determining; Glu-570 is the proposed general base catalyst.\",\n      \"method\": \"Bi-substrate kinetic analysis, product inhibition, equilibrium dialysis, pre-steady-state quench-flow, pH-dependent activity measurements\",\n      \"journal\": \"Biochemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — rigorous multi-method in vitro mechanistic enzymology establishing catalytic mechanism\",\n      \"pmids\": [\"11009610\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"P/CAF auto-acetylates itself intramolecularly at five lysines (416–442) within its nuclear localization signal (NLS) at the C-terminus, and intermolecularly via its N-terminal domain; P/CAF is also acetylated by p300 but not CBP; auto-acetylation increases PCAF HAT activity.\",\n      \"method\": \"In vitro acetylation assay, mutational analysis, in vivo acetylation detection\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — in vitro assay with mutagenesis, single lab, no independent replication cited\",\n      \"pmids\": [\"12888487\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"P/CAF autoacetylation at the NLS (C-terminal lysines) controls its nuclear localization; HAT-inactive P/CAF accumulates in the cytoplasm; HDAC3 (and to a lesser extent HDAC1/2/4) deacetylates P/CAF leading to cytoplasmic accumulation; P/CAF accumulates in cytoplasm during apoptosis.\",\n      \"method\": \"Subcellular fractionation, fluorescence microscopy, HAT-dead mutant, HDAC overexpression/knockdown\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct localization by imaging and fractionation with functional mutant analysis, single lab\",\n      \"pmids\": [\"19015268\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"PCAF interacts physically with PTEN and acetylates PTEN at Lys125 and Lys128 within its catalytic cleft in a growth-factor-dependent manner, reducing PTEN's lipid phosphatase activity and thereby maintaining PI3K/AKT signaling; acetylation-resistant K125R/K128R mutants retain PI3K-suppressing and G1 arrest activities even with PCAF overexpression.\",\n      \"method\": \"Co-immunoprecipitation, in vitro acetyltransferase assay, shRNA knockdown, acetylation-resistant mutant analysis, cell cycle assays\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Moderate — in vitro acetylation, acetylation-site mutagenesis with functional readout, shRNA rescue, single lab but multiple orthogonal methods\",\n      \"pmids\": [\"16829519\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"PCAF possesses an intrinsic ubiquitin E3 ligase activity (distinct from its acetyltransferase activity) that ubiquitinates Hdm2, promoting its degradation and thereby stabilizing p53; PCAF knockdown stabilizes Hdm2.\",\n      \"method\": \"PCAF knockdown in HeLa/U2OS cells, in vitro ubiquitination assay, domain deletion analysis\",\n      \"journal\": \"Nature cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Strong — in vitro ubiquitination assay plus cellular knockdown phenotype, mechanistically distinct activity characterized\",\n      \"pmids\": [\"17293853\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2002,\n      \"finding\": \"PCAF acetylates HIV-1 Tat at Lys50; acetylated Tat binds the PCAF bromodomain; structural analysis defined critical interaction residues (Y47/R53 in Tat; V763/Y802/Y809 in PCAF bromodomain); mutations at these residues cumulatively inhibit Tat–PCAF interaction and synergistic HIV promoter activation.\",\n      \"method\": \"In vitro binding assay, in vivo co-immunoprecipitation, structural analysis of acetyl-peptide–bromodomain complex, site-directed mutagenesis, HIV promoter reporter assay\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — structural data plus mutagenesis plus functional reporters; multiple orthogonal methods\",\n      \"pmids\": [\"12032084\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2000,\n      \"finding\": \"P/CAF directly interacts with Smad3 (via Smad3 MH2 domain and P/CAF N-terminal region) upon TGF-β receptor activation; P/CAF potentiates TGF-β/Smad3-mediated transcription cooperatively with p300 and Smad4.\",\n      \"method\": \"In vitro GST pull-down, co-immunoprecipitation in mammalian cells, transcription reporter assays\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal in vitro and in vivo binding plus functional reporters, single lab\",\n      \"pmids\": [\"11058129\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2000,\n      \"finding\": \"P/CAF-mediated acetylation of TAL1/SCL maps to a lysine-rich motif in the loop region and increases TAL1 DNA binding while selectively inhibiting its interaction with co-repressor mSin3A; an acetylation-defective P/CAF mutant inhibits TAL1 acetylation, DNA binding, transcription, and terminal erythroid differentiation.\",\n      \"method\": \"In vitro acetylation assay, domain mapping, DNA-binding EMSA, co-immunoprecipitation, differentiation assay with HAT-dead mutant\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Strong — in vitro enzymatic assay, site mapping, EMSA, co-IP, and cell differentiation phenotype all converge\",\n      \"pmids\": [\"11118214\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2000,\n      \"finding\": \"Mice lacking PCAF are developmentally normal; in PCAF-null mice, PCAF-B/GCN5 protein levels are drastically elevated in tissues where PCAF is normally abundant, indicating functional compensation between PCAF and GCN5.\",\n      \"method\": \"Gene knockout mouse model, Western blot quantification of compensatory protein levels\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — clean knockout genetic model with biochemical compensation measured in multiple tissues\",\n      \"pmids\": [\"11027331\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2001,\n      \"finding\": \"Cyclin D1 and the androgen receptor (AR) both bind overlapping domains of P/CAF; cyclin D1 displaces AR binding to P/CAF in vitro; the HAT activity of P/CAF rescues cyclin D1-mediated AR trans-repression.\",\n      \"method\": \"In vitro binding/displacement assay, HAT-dead P/CAF rescue experiment, reporter assays\",\n      \"journal\": \"Molecular endocrinology (Baltimore, Md.)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vitro competitive binding plus HAT-dead rescue in reporter assays; single lab\",\n      \"pmids\": [\"11328859\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1999,\n      \"finding\": \"Cyclin D1 interacts with the histone acetyltransferase P/CAF, facilitating P/CAF–estrogen receptor (ER) association; P/CAF potentiates cyclin D1-stimulated ER transcriptional activity in a dose-dependent, HAT-activity-dependent manner.\",\n      \"method\": \"Co-immunoprecipitation, reporter assay, HAT-dead mutant analysis\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — co-IP and HAT-dead functional test, single lab\",\n      \"pmids\": [\"10318892\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"P/CAF acetylates the ETS transcription factor ER81 at K116 (and p300 additionally at K33); acetylation enhances ER81 transactivation, DNA binding activity, and in vivo half-life; oncogenic HER2/Neu stimulates p300-mediated ER81 acetylation via the Ras→Raf→MAPK pathway.\",\n      \"method\": \"In vitro and in vivo acetylation assay, acetylation-deficient mutant analysis, DNA binding assay, protein stability measurement\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1–2 / Moderate — in vitro acetylation with site mutagenesis plus in vivo functional tests; single lab\",\n      \"pmids\": [\"12917345\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1998,\n      \"finding\": \"NF-Y complex associates with human GCN5 and P/CAF in vivo and possesses HAT activity through these interactions; the NF-YB:YC histone-fold motif is sufficient for stable interaction with GCN5 in vitro; deletion of N- or C-terminal regions of GCN5 disrupts NF-Y interaction.\",\n      \"method\": \"In vivo co-immunoprecipitation, in vitro interaction assay, deletion mutant analysis, transient transfection reporter assay\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vitro and in vivo binding with domain mapping and functional reporter; single lab\",\n      \"pmids\": [\"9430679\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2002,\n      \"finding\": \"The adenovirus E1B 55-kDa oncoprotein specifically inhibits PCAF-mediated acetylation of p53 at K320 in vivo and in vitro (without affecting histone acetylation or PCAF autoacetylation) by physically binding PCAF and interfering with the PCAF–p53 interaction.\",\n      \"method\": \"In vitro acetylation assay, co-immunoprecipitation, competition assay, in vivo acetylation measurement\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1–2 / Moderate — in vitro and in vivo enzymatic inhibition with binding competition mechanism; single lab\",\n      \"pmids\": [\"10891493\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2002,\n      \"finding\": \"MDM2 interacts with PCAF in vitro and in cells and inhibits PCAF-mediated acetylation of p53 at K320 in vitro and in overexpression experiments, repressing PCAF-dependent p53 transcriptional activation without affecting p53 levels.\",\n      \"method\": \"GST pull-down, co-immunoprecipitation, in vitro acetylation assay, reporter assay, chromatin immunoprecipitation\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vitro and in vivo binding plus in vitro enzymatic inhibition; single lab\",\n      \"pmids\": [\"12068014\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"PCAF associates with actin and hnRNP U in nuclear extracts via affinity chromatography and protein-protein interaction assays; PCAF-associated HAT activity is released by disruption of the actin–hnRNP U complex; PCAF, actin, and hnRNP U co-occupy promoters and coding regions of pol II genes and associate with nascent ribonucleoprotein complexes, supporting a role for PCAF in pol II transcription elongation.\",\n      \"method\": \"Affinity chromatography, co-immunoprecipitation, biochemical fractionation, chromatin immunoprecipitation, RNA immunoprecipitation, bromouridine incorporation assay\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple biochemical methods in single lab; functional elongation link from hnRNP U disruption assay\",\n      \"pmids\": [\"18710935\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"PCAF and HDAC4 associate with cardiac sarcomeres (Z-disc and I/A bands) in cardiomyocytes; PCAF acetylates the Z-disc protein MLP (muscle LIM protein); increased acetylation via HDAC inhibition enhances myofilament calcium sensitivity in wild-type but not MLP-knockout mice.\",\n      \"method\": \"Immunohistochemistry, electron microscopy, co-immunoprecipitation, in vitro acetylation assay, calcium sensitivity measurement, knockout comparison\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct localization, in vitro acetylation, and MLP-KO genetic control; single lab\",\n      \"pmids\": [\"18250163\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"PCAF acetylates β-catenin, inhibiting its ubiquitination and increasing its stability; the key ubiquitination sites K19 and K49 of β-catenin are the critical residues for PCAF-induced acetylation and stabilization; PCAF knockdown reduces β-catenin protein level, transcriptional activity, promotes differentiation, and inhibits migration.\",\n      \"method\": \"Co-immunoprecipitation, in vitro acetylation assay, site-directed mutagenesis, ubiquitination assay, shRNA knockdown, cell migration and differentiation assays\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Moderate — in vitro acetylation, site mutagenesis, ubiquitination competition, and loss-of-function phenotype; multiple orthogonal methods in single lab\",\n      \"pmids\": [\"18987336\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"PCAF/KAT2B interacts with GLI1 (downstream effector of Hedgehog signaling) and is required for H3K9 acetylation on Hh target gene promoters; PCAF depletion impairs Hh target gene expression, reduces medulloblastoma/glioblastoma cell proliferation, and reduces tumor-forming potential of neural stem cells in vivo.\",\n      \"method\": \"Co-immunoprecipitation, siRNA knockdown, ChIP for H3K9ac, proliferation assay, apoptosis assay, in vivo neural stem cell tumor assay\",\n      \"journal\": \"Cancer research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — co-IP, ChIP, and in vivo assay; single lab, no in vitro reconstitution of direct acetylation\",\n      \"pmids\": [\"23943798\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"PCAF acts as a novel E3 ubiquitin ligase for GLI1; in response to genotoxic stress, p53-elevated PCAF promotes GLI1 ubiquitination and proteasome-dependent degradation (requires the ubiquitination domain of PCAF, not a deletion mutant lacking it), thereby inhibiting Hedgehog signaling.\",\n      \"method\": \"In vitro ubiquitination assay, deletion mutant of PCAF ubiquitination domain, shRNA knockdown of p53/PCAF, GLI1 rescue experiment, in vivo medulloblastoma model\",\n      \"journal\": \"Cell death and differentiation\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Moderate — in vitro ubiquitination assay, domain-deletion specificity control, genetic rescue, in vivo tumor model; single lab but multiple strong methods\",\n      \"pmids\": [\"24013724\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"KAT2B (PCAF) is recruited by dephosphorylated CRTC2 to gluconeogenic gene promoters, where it acetylates H3K9 (H3K9Ac); KAT2B cooperates with WDR5 to stimulate the gluconeogenic program; depletion of KAT2B or WDR5 decreases gluconeogenic gene expression and a KAT2B antagonist lowers blood glucose in insulin-resistant mice.\",\n      \"method\": \"Mouse knockout/knockdown models, in vitro acetylation assays, ChIP, small-molecule KAT2B inhibitor in vivo\",\n      \"journal\": \"The Journal of clinical investigation\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Strong — in vitro assay plus in vivo genetic and pharmacological validation across multiple model systems\",\n      \"pmids\": [\"24051374\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"KAT2A and KAT2B (PCAF) acetylate PLK4 kinase domain at K45 and K46; K45/K46 acetylation impairs PLK4 kinase activity in vitro (molecular dynamics suggests shift to inactive conformation); the PLK4 K45R/K46R mutant does not cause centrosome overamplification when overexpressed; impairing KAT2A/2B acetyltransferase activity results in excess centrosome numbers in cells.\",\n      \"method\": \"Shotgun proteomics acetylome, in vitro kinase assay after acetylation, molecular dynamics modelling, mutant overexpression centrosome assay\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — proteomics substrate identification, in vitro enzymatic assay with mutagenesis, and cellular phenotypic validation; multiple orthogonal methods\",\n      \"pmids\": [\"27796307\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"PCAF acetylates PGC-1α at K328 and K450, triggering its proteasomal degradation and suppressing gluconeogenic transcriptional activity; adenoviral PCAF expression in obese mouse liver represses gluconeogenic enzyme activation and improves glucose homeostasis; liver-specific PCAF knockdown increases blood glucose.\",\n      \"method\": \"In vitro acetylation assay, site-directed mutagenesis, adenoviral overexpression in vivo, liver-specific knockdown, glucose tolerance tests\",\n      \"journal\": \"Cell reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Strong — in vitro enzymatic assay with site mapping, in vivo genetic gain/loss-of-function, metabolic phenotype; multiple methods single lab\",\n      \"pmids\": [\"25497092\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"PCAF acetylates EZH2 primarily at K348; K348 acetylation decreases EZH2 phosphorylation at T345 and T487, increases EZH2 stability without disrupting PRC2 formation, and enhances EZH2's capacity to suppress target genes; SIRT1 deacetylates EZH2.\",\n      \"method\": \"Co-immunoprecipitation, in vitro acetylation assay, site-directed mutagenesis, protein stability assay, PRC2 complex immunoprecipitation\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1–2 / Moderate — in vitro acetylation with site mapping, mutagenesis, complex analysis; single lab\",\n      \"pmids\": [\"25800736\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"PCAF directly interacts with cdk2; PCAF inhibits cyclin/cdk2 activity by two mechanisms: (i) disrupting cyclin–cdk2 interaction and (ii) acetylating cdk2 at K33 (within the ATP-binding pocket), thereby inhibiting cdk2 kinase activity; PCAF overexpression arrests cells at S and G2/M in a cdk2-dependent manner.\",\n      \"method\": \"Co-immunoprecipitation, in vitro kinase assay, in vitro acetylation with K33 mutagenesis, cell cycle analysis, cdk2 rescue overexpression\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1–2 / Moderate — in vitro acetylation with site mutagenesis plus cell cycle functional assay; single lab\",\n      \"pmids\": [\"19773423\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"During keratinocyte differentiation, PCAF acetylates Rb at sites within its nuclear localization sequence; PCAF HAT activity is required for normal differentiation; acetylation-deficient Rb is mislocalized to the cytoplasm during differentiation, and SIRT1 overexpression or PCAF reduction causes the same Rb mislocalization.\",\n      \"method\": \"shRNA depletion, HAT-dead PCAF, acetylation-site Rb mutants, subcellular fractionation/immunofluorescence, differentiation assays\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct localization experiment tied to functional consequence, site-specific mutant analysis; single lab\",\n      \"pmids\": [\"20940255\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"PCAF is an HIF-1α cofactor that acetylates HIF-1α under hypoxia-mimicking conditions; PCAF-mediated acetylation of p53 at K320 is preferentially reduced under hypoxia compared to K382 acetylation (by p300), redirecting acetylated p53 to p21 promoters while preventing recruitment to pro-apoptotic BID promoter.\",\n      \"method\": \"Co-immunoprecipitation, chromatin immunoprecipitation, acetylation site-specific analysis under hypoxia\",\n      \"journal\": \"Oncogene\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — ChIP and co-IP analysis of promoter-specific recruitment; site-specific acetylation under hypoxia; single lab\",\n      \"pmids\": [\"18574470\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"PCAF HAT activity is required for stress-induced H3K9 and H3K14 acetylation at the p21 promoter and for p53-dependent p21 transcription in response to multiple stresses (nutlin-3, DNA damage, p14ARF); this role is independent of p53 K320 acetylation; PCAF loss prevents cell cycle arrest.\",\n      \"method\": \"siRNA knockdown, HAT-dead PCAF mutant, chromatin immunoprecipitation for H3K9ac/H3K14ac, p53 promoter occupancy assay, cell cycle analysis\",\n      \"journal\": \"Cell cycle (Georgetown, Tex.)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — ChIP for specific histone marks, HAT-dead mutant, loss-of-function cell cycle phenotype; single lab\",\n      \"pmids\": [\"22713239\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"PCAF/GCN5 PCAF-deficient macrophages exhibit markedly reduced cytokine production upon LPS stimulation; chemical inhibition of PCAF/GCN5 bromodomains alone is insufficient to recapitulate this immune phenotype, but PCAF/GCN5 PROTAC-mediated degradation potently modulates inflammatory mediator expression.\",\n      \"method\": \"PCAF-deficient macrophage functional assay, bromodomain inhibitor comparison, PROTAC-mediated degradation, cytokine expression assay\",\n      \"journal\": \"ACS chemical biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic KO plus pharmacological PROTAC comparator; demonstrates bromodomain vs. scaffolding/enzymatic activity distinction; single lab\",\n      \"pmids\": [\"30200762\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"PCAF acetylates RPA1 at K163; DNA-PK phosphorylates and activates PCAF upon UV damage to promote K163 acetylation; K163 acetylation of RPA1 is critical for accumulation of XPA at damaged DNA and activation of nucleotide excision repair (NER) specifically; HDAC6 and SIRT1 deacetylate RPA1.\",\n      \"method\": \"In vitro acetylation assay, co-immunoprecipitation, site-directed mutagenesis, NER assay, XPA recruitment to damage sites, HDAC identification\",\n      \"journal\": \"Cell reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Strong — in vitro acetylation with site mapping, upstream kinase (DNA-PK) identified, eraser (HDAC6/SIRT1) identified, pathway-specific functional assay (NER vs other repair); multiple orthogonal methods\",\n      \"pmids\": [\"28854354\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"PCAF is a fork-associated protein at stalled replication forks; PCAF acetylates H4K8 at stalled forks, recruiting MRE11 and EXO1 (via an H4K8ac-binding domain) to promote fork degradation in BRCA-deficient cells; ATR phosphorylates PCAF at S264 to limit its fork association and activity; low PCAF levels stabilize stalled forks and cause PARPi resistance in BRCA-deficient cells.\",\n      \"method\": \"Chromatin fractionation at forks, in vitro H4K8 acetylation assay, S264 phospho-site mapping, MRE11/EXO1 H4K8ac binding domain analysis, PARPi resistance assay, ATR inhibition\",\n      \"journal\": \"Molecular cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Strong — in vitro acetylation, binding domain mapping, upstream regulator (ATR) identified, functional fork stability/PARPi resistance readout; rigorous multi-method single lab\",\n      \"pmids\": [\"32966758\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"hSIRT1 deacetylates PCAF in vitro and modulates PCAF acetylation in vivo; hSIRT1 represses E2F1-dependent p73 promoter activity by forming a hSIRT1–PCAF–E2F1 complex on the P1p73 promoter; upon apoptotic DNA damage, decreased nuclear NAD+ inactivates hSIRT1's deacetylase activity (without disrupting SIRT1–PCAF interaction), releasing PCAF to form active PCAF/E2F1 complexes on the P1p73 promoter.\",\n      \"method\": \"In vitro deacetylation assay, co-immunoprecipitation, chromatin immunoprecipitation, NAD+ manipulation, reporter assay\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1–2 / Moderate — in vitro deacetylation plus ChIP and co-IP; single lab but mechanistic detail of NAD+ regulation tested\",\n      \"pmids\": [\"19188449\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"PTH treatment increases PCAF acetylation at the MMP-13 promoter in a p300-dependent manner; p300-dependent PCAF acetylation and mutual p300–PCAF promoter recruitment is required for PTH-induced MMP-13 transcription; HAT activities of both PCAF and p300 are additively required.\",\n      \"method\": \"ChIP, siRNA knockdown of PCAF/p300/Runx2, reporter assay with HAT-dead mutants\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — ChIP, siRNA knockdown, and HAT-dead mutant analyses; single lab\",\n      \"pmids\": [\"20870727\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"PCAF directly acetylates cytoplasmic GLI1 at K518, preventing its nuclear translocation and promoter occupancy, suppressing Hedgehog signaling in hepatocellular carcinoma; PCAF-mediated GLI1 acetylation reduces BCL2 expression and upregulates BAX.\",\n      \"method\": \"In vitro acetylation assay, site-directed mutagenesis, subcellular fractionation, ChIP, in vivo xenograft model\",\n      \"journal\": \"Cell death & disease\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1–2 / Moderate — in vitro acetylation with site mapping, localization assay, and in vivo tumor model; single lab\",\n      \"pmids\": [\"25855960\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"GCN5L (KAT2B) stably associates with Mediator containing the cdk8 subcomplex (T/G-Mediator) together with TRRAP; cdk8 phosphorylates H3 serine-10, which then stimulates H3K14 acetylation by GCN5L within the complex, producing tandem H3 phosphoacetylation that correlates with transcriptional activation.\",\n      \"method\": \"Reconstituted human transcription system, co-immunoprecipitation, in vitro histone modification assay, cdk8 knockdown, ChIP\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — reconstituted in vitro transcription/modification system plus cellular ChIP validation; rigorous biochemical dissection\",\n      \"pmids\": [\"18418385\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"PCAF (Kat2b) and Gcn5 negatively regulate IFN-β production through a HAT-independent, non-transcriptional mechanism by inhibiting the innate immune kinase TBK1 in the cytoplasm; Gcn5/PCAF-mediated H3K9ac is dispensable for IFNB expression and the vast majority of active genes in fibroblasts.\",\n      \"method\": \"HAT-dead mutant analysis, cytoplasmic TBK1 inhibition assay, genetic knockout of Gcn5/PCAF, IFN-β production assay\",\n      \"journal\": \"EMBO reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — HAT-dead mutant dissects HAT-independent function; cytoplasmic TBK1 inhibition demonstrated; single lab\",\n      \"pmids\": [\"25269644\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"PCAF acetylates HOXA10 at K338 and K339, inhibiting HOXA10-mediated ITGB3 (β3-integrin) transcription and thereby impairing endometrial receptivity and embryo adhesion.\",\n      \"method\": \"Co-immunoprecipitation, in vitro acetylation assay with site mapping, luciferase reporter assay, ChIP, BeWo spheroid attachment assay, PCAF overexpression/knockdown\",\n      \"journal\": \"The Journal of clinical endocrinology and metabolism\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1–2 / Moderate — in vitro acetylation with site mapping, ChIP, functional adhesion assay; single lab\",\n      \"pmids\": [\"24037888\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"PCAF directly interacts with p27Kip1 (via aa 91–120 of p27; PCAF catalytic domain required) and acetylates p27 at K100; PCAF overexpression induces proteasomal degradation of p27 (Skp2-independent); K100R mutant p27 is resistant to PCAF-induced degradation and remains stable through the cell cycle.\",\n      \"method\": \"Co-immunoprecipitation, in vitro acetylation assay, K100R mutagenesis, protein half-life measurement, proteasome inhibitor assay, ubiquitylation assay\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1–2 / Moderate — in vitro acetylation with site mutagenesis, proteasomal pathway confirmed; single lab\",\n      \"pmids\": [\"22547391\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"PCAF-dependent acetylation of ISX at K69 promotes ISX interaction with BRD4 (acetylated at K332) and nuclear translocation of the ISX–BRD4 complex; in the nucleus, the complex binds EMT gene promoters with H3K9/K14/K18 acetylation, activating EMT transcription and cancer metastasis.\",\n      \"method\": \"Co-immunoprecipitation, site-directed mutagenesis, subcellular fractionation, ChIP, histone acetylation analysis\",\n      \"journal\": \"EMBO reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — co-IP, mutagenesis, ChIP, and nuclear localization assays; single lab\",\n      \"pmids\": [\"31908141\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"SIRT7 directly interacts with PCAF and deacetylates PCAF at K720 upon glucose deprivation; deacetylated PCAF binds MDM2 more strongly, promoting MDM2 ubiquitination/degradation, elevating p53, and inducing p21/cell-cycle arrest.\",\n      \"method\": \"Co-immunoprecipitation, in vitro deacetylation assay, K720 site mapping, MDM2 ubiquitination assay, cell cycle analysis\",\n      \"journal\": \"Oncogene\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1–2 / Moderate — in vitro deacetylation assay, site-specific mutagenesis, downstream ubiquitination assay; single lab\",\n      \"pmids\": [\"32404984\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"PCAF interacts with GLI1 and ubiquitinates it (E3 ubiquitin ligase activity), inhibiting HCC cell metastasis and EMT; PCAF-mediated GLI1 targeting suppresses Gli1-driven EMT in hepatocellular carcinoma.\",\n      \"method\": \"Co-immunoprecipitation, in vitro ubiquitination assay, siRNA knockdown, migration/invasion assay\",\n      \"journal\": \"Cancer letters\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — co-IP plus in vitro ubiquitination plus cellular functional assay; single lab\",\n      \"pmids\": [\"26945969\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"PCAF acetylates MKL1 in response to pro-inflammatory stimuli (TNF-α, LPS); acetylation promotes MKL1 nuclear enrichment, enhances MKL1–NF-κB interaction, and stabilizes MKL1 binding to NF-κB target promoters, activating pro-inflammatory transcription.\",\n      \"method\": \"Co-immunoprecipitation, in vivo acetylation analysis, MKL1 lysine mutant functional assay, nuclear fractionation, ChIP\",\n      \"journal\": \"Biochimica et biophysica acta. Gene regulatory mechanisms\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — co-IP, acetylation mutant, ChIP, and nuclear localization analysis; single lab\",\n      \"pmids\": [\"28571745\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"PCAF regulates the EB1–TIP150 interaction at kinetochore microtubule plus ends by acetylating EB1; persistent EB1 acetylation by PCAF perturbs the EB1–TIP150 interaction, leading to metaphase alignment defects, spindle checkpoint activation, and chromosome aneuploidy.\",\n      \"method\": \"siRNA knockdown, co-immunoprecipitation, acetylation assay, live cell imaging of chromosome alignment, spindle checkpoint assay\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — co-IP, acetylation assay, and cellular kinetochore phenotype; single lab\",\n      \"pmids\": [\"23595990\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"PCAF (and GCN5) acetylate influenza A virus nucleoprotein (NP) in vitro; PCAF acetylates NP at Lys-31 while GCN5 targets Lys-90; PCAF silencing increases viral polymerase activity, indicating that PCAF-mediated NP acetylation at K31 negatively regulates influenza replication.\",\n      \"method\": \"In vitro acetyltransferase assay, LC-MS site identification, RNAi silencing, viral polymerase activity assay\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — in vitro enzymatic assay with MS site mapping plus RNAi functional test; single lab\",\n      \"pmids\": [\"29555684\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"PCAF binds p73; the N-terminal transactivation domain and OD of p73 and the HAT domain of PCAF are required for interaction; PCAF HAT activity is required for stimulating p73-mediated transactivation of p21 and induction of apoptosis.\",\n      \"method\": \"Co-immunoprecipitation, domain mapping, reporter assay, PCAF-specific siRNA, colony formation assay\",\n      \"journal\": \"Oncogene\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — co-IP domain mapping, HAT-dead mutant, and siRNA functional test; single lab\",\n      \"pmids\": [\"14614455\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"PCAF and CBP/p300 are repressed by inhibitory (myelin, CSPG) substrates in neurons; HDAC inhibition restores PCAF/CBP/p300 expression; PCAF and CBP/p300 acetylate histone H3 at K9–14 and p53, initiating a pro-neuronal outgrowth transcriptional program that promotes axon growth and counteracts growth cone collapse.\",\n      \"method\": \"Gene silencing, gain-of-function, chromatin acetylation analysis, neurite outgrowth quantification\",\n      \"journal\": \"Cell death and differentiation\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — loss/gain-of-function with acetylation readout and outgrowth phenotype; single lab\",\n      \"pmids\": [\"20094059\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"Gcn5 and PCAF double knockout blocks PPARγ expression (preventing adipocyte differentiation) and is essential for Prdm16 expression (required for brown adipogenesis); Gcn5/PCAF facilitate PPARγ RNA pol II recruitment and Prdm16 transcript elongation.\",\n      \"method\": \"Double-knockout cell lines, PPARγ rescue expression, ChIP for pol II, nascent RNA analysis\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — double-KO genetic model with ChIP and rescue experiments; single lab\",\n      \"pmids\": [\"25071153\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"HIPK2 cooperates with PCAF to induce PCAF-mediated p53 acetylation after nonapoptotic DNA damage; HIPK2 depletion abolishes PCAF-dependent p53 acetylation and reduces p53 binding to the p21Waf1 promoter, inhibiting p21 transactivation and allowing cell proliferation.\",\n      \"method\": \"RNAi knockdown of HIPK2, ChIP, acetylation analysis, cell cycle assay\",\n      \"journal\": \"Oncogene\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — epistasis via RNAi knockdown, ChIP, and acetylation site analysis; single lab\",\n      \"pmids\": [\"15897882\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"KAT2B (PCAF) is a lysine acetyltransferase (GNAT superfamily) that operates via an ordered Bi-Bi mechanism with acetyl-CoA binding first, targeting histone H3K9/K14 and a broad range of non-histone substrates including p53 (K320), β-catenin, PLK4 (K45/K46), RPA1 (K163), PGC-1α, PTEN, EZH2, cdk2 (K33), GLI1 (K518), MKL1, Rb, and others; it also possesses a distinct intrinsic E3 ubiquitin ligase activity targeting Hdm2 and GLI1; its nuclear localization is regulated by autoacetylation of its NLS (deacetylated by HDAC3/SIRT1 causing cytoplasmic accumulation); its acetyltransferase activity is activated by auto-acetylation and p300-mediated acetylation, inhibited by viral oncoproteins (E1A, E1B-55K), MDM2, and DEK, and regulated by ATR phosphorylation at S264 at stalled replication forks; PCAF participates in large multiprotein complexes (STAGA/TFTC/ATAC) and cooperates with p300/CBP as a transcriptional co-activator for nuclear receptors, MyoD, Notch/RBP-J, Smads, p73, GLI1, and other factors, while also functioning as a HAT-independent cytoplasmic inhibitor of TBK1 to negatively regulate innate IFN-β production.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"KAT2B (PCAF) is a GNAT-family lysine acetyltransferase that functions as a transcriptional co-activator and broad-spectrum protein-modifying enzyme, coupling chromatin acetylation to the control of cell differentiation, cell-cycle progression, genome maintenance, and metabolism [#6, #7, #1]. Mechanistically it catalyzes acetyl transfer through a fully ordered Bi-Bi mechanism in which acetyl-CoA binds first and acetyl transfer to histone H3 Lys-14 is rate-determining, with Glu-570 acting as the proposed general base; its extended N-terminal domain (relative to yeast Gcn5p) enables acetylation of nucleosomal as well as free histones [#7, #6]. On chromatin, KAT2B deposits H3K9/H3K14 acetylation cooperatively with p300/CBP and within larger machines, including a cdk8-containing Mediator complex where H3 Ser-10 phosphorylation stimulates KAT2B-mediated H3K14 acetylation to produce activating tandem phosphoacetylation [#41, #6]. Through direct interactions it serves as a co-activator for diverse transcription factors and signaling effectors—MyoD-driven myogenesis and p21 induction, nuclear receptors, TGF-\\u03b2/Smad3, Notch/RBP-J, p73, and GLI1—frequently requiring its intrinsic HAT activity [#1, #2, #13, #5, #51, #25]. Beyond histones, KAT2B acetylates a wide range of non-histone substrates to alter their activity, stability, or localization: p53 at K320 to enhance DNA binding after damage [#0], PTEN at K125/K128 to dampen its lipid-phosphatase activity and sustain PI3K/AKT signaling [#10], \\u03b2-catenin at ubiquitination sites K19/K49 to block its degradation [#24], EZH2 at K348 to stabilize it [#30], cdk2 at K33 and p27 at K100 to restrain cell-cycle kinases [#31, #44], PLK4 at K45/K46 to limit centrosome amplification [#28], PGC-1\\u03b1 to trigger its degradation and suppress gluconeogenesis [#29], and RPA1 at K163 to drive nucleotide excision repair [#36]. KAT2B also carries a mechanistically distinct intrinsic E3 ubiquitin ligase activity that ubiquitinates Hdm2 (stabilizing p53) and GLI1 (terminating Hedgehog signaling) [#11, #26]. At the genome it acts at stalled replication forks, where it acetylates H4K8 to recruit MRE11/EXO1 and promote fork degradation, an activity restrained by ATR phosphorylation at S264 [#37]. Its own nuclear localization is governed by autoacetylation of a C-terminal NLS, which is reversed by HDAC3/SIRT1 to drive cytoplasmic accumulation [#9, #8], and a cytoplasmic, HAT-independent pool inhibits the kinase TBK1 to negatively regulate IFN-\\u03b2 production [#42]. KAT2B is functionally redundant with GCN5, which is upregulated in PCAF-null mice to compensate [#15].\"\n,\n  \"teleology\": [\n    {\n      \"year\": 1998,\n      \"claim\": \"Established that human PCAF/GCN5 differ from yeast Gcn5p by acetylating nucleosomal substrates, defining KAT2B as a bona fide chromatin-modifying enzyme that partners with CBP/p300.\",\n      \"evidence\": \"In vitro HAT assays on free versus nucleosomal histones with comparative domain analysis\",\n      \"pmids\": [\"9742083\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not resolve which complexes target it to chromatin in vivo\", \"Substrate site specificity on nucleosomes not fully mapped\"]\n    },\n    {\n      \"year\": 2000,\n      \"claim\": \"Defined the catalytic mechanism, showing KAT2B uses an ordered Bi-Bi mechanism with acetyl-CoA binding first and acetyl transfer as the rate-limiting chemical step.\",\n      \"evidence\": \"Bi-substrate kinetics, product inhibition, equilibrium dialysis, and pre-steady-state quench-flow on H3 peptide\",\n      \"pmids\": [\"11009610\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Kinetics established on peptide, not full nucleosomes\", \"General-base role of Glu-570 inferred, not structurally proven in this study\"]\n    },\n    {\n      \"year\": 1997,\n      \"claim\": \"Showed KAT2B HAT activity is specifically required for terminal differentiation, linking its enzymatic function to p21 induction and cell-cycle exit in myogenesis.\",\n      \"evidence\": \"Anti-PCAF antibody microinjection, HAT-dead mutant, and reporter assays in muscle differentiation\",\n      \"pmids\": [\"9659901\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct substrates driving p21 induction not pinned to histone vs non-histone\", \"Did not separate PCAF from GCN5 contribution\"]\n    },\n    {\n      \"year\": 1999,\n      \"claim\": \"Identified the first non-histone substrate, p53 at K320, showing acetylation enhances p53 DNA binding and is induced by DNA damage—extending KAT2B function beyond chromatin.\",\n      \"evidence\": \"In vitro acetyltransferase assay with site-specific antibodies and in vivo detection after genotoxic stress\",\n      \"pmids\": [\"9891054\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Erasers of K320 not identified here\", \"In vivo functional consequence for specific target genes not resolved\"]\n    },\n    {\n      \"year\": 1999,\n      \"claim\": \"Demonstrated that viral and cellular antagonists directly inhibit KAT2B, establishing it as a regulated node; E1A, E1B-55K, and MDM2 bind PCAF and block its acetylation of p53.\",\n      \"evidence\": \"Direct binding and in vitro/in vivo HAT inhibition assays for E1A, E1B-55K, and MDM2\",\n      \"pmids\": [\"10025405\", \"10891493\", \"12068014\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural basis of inhibition not fully resolved\", \"Whether inhibition is global or substrate-selective varies by antagonist\"]\n    },\n    {\n      \"year\": 2000,\n      \"claim\": \"Genetically established functional redundancy between KAT2B and GCN5, explaining the viability of PCAF-null animals.\",\n      \"evidence\": \"PCAF-knockout mouse with Western quantification of compensatory GCN5 upregulation\",\n      \"pmids\": [\"11027331\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not identify non-redundant KAT2B-specific functions in vivo\", \"Tissue-specific requirements not dissected\"]\n    },\n    {\n      \"year\": 2003,\n      \"claim\": \"Showed KAT2B activity and localization are self-regulated by autoacetylation, with p300 also acetylating it and autoacetylation boosting HAT activity.\",\n      \"evidence\": \"In vitro and in vivo acetylation assays with NLS-lysine mutagenesis\",\n      \"pmids\": [\"12888487\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single lab without independent replication\", \"Quantitative contribution of inter- vs intramolecular autoacetylation unclear\"]\n    },\n    {\n      \"year\": 2008,\n      \"claim\": \"Connected autoacetylation to subcellular control, showing NLS acetylation drives nuclear retention while HDAC3/SIRT1 deacetylation causes cytoplasmic accumulation.\",\n      \"evidence\": \"Subcellular fractionation, imaging, HAT-dead mutants, and HDAC manipulation\",\n      \"pmids\": [\"19015268\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Signals triggering deacetylation-driven export not defined\", \"Single lab\"]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"Revealed a second, mechanistically distinct enzymatic activity: an intrinsic E3 ubiquitin ligase that ubiquitinates Hdm2 to stabilize p53.\",\n      \"evidence\": \"In vitro ubiquitination assay plus knockdown phenotype with domain deletion\",\n      \"pmids\": [\"17293853\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Catalytic ubiquitin-ligase residues not fully mapped\", \"Relationship between HAT and E3 domains structurally unresolved\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Extended the dual-enzyme model to Hedgehog signaling, showing KAT2B both supports GLI1-dependent H3K9ac on target promoters and ubiquitinates/acetylates GLI1 to terminate or restrain the pathway.\",\n      \"evidence\": \"Co-IP, ChIP, in vitro ubiquitination/acetylation, site mutagenesis, and in vivo tumor models\",\n      \"pmids\": [\"23943798\", \"24013724\", \"25855960\", \"26945969\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Context determining co-activator vs degradative role not resolved\", \"Direct GLI1 acetylation not reconstituted in every report\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Broadened the non-histone substrate repertoire to cell-cycle and centrosome control, identifying acetylation of cdk2 (K33), p27 (K100), and PLK4 (K45/K46) as inhibitory modifications.\",\n      \"evidence\": \"Acetylome proteomics, in vitro acetylation with site mutagenesis, kinase assays, and centrosome/cell-cycle phenotypes\",\n      \"pmids\": [\"27796307\", \"22547391\", \"19773423\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Endogenous stoichiometry of these acetylations unclear\", \"Erasers not identified for all sites\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Established KAT2B as a metabolic regulator of hepatic gluconeogenesis through both histone and non-histone routes, with pharmacological tractability for glycemic control.\",\n      \"evidence\": \"In vitro acetylation, ChIP, liver-specific knockdown/overexpression, and small-molecule inhibitor in metabolic mouse models\",\n      \"pmids\": [\"24051374\", \"25497092\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Reconciliation of gluconeogenesis-promoting (H3K9ac/CRTC2) and -suppressing (PGC-1\\u03b1 degradation) roles not fully integrated\", \"Tissue selectivity of inhibitor not detailed\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Placed KAT2B in the DNA-damage response, showing DNA-PK-activated KAT2B acetylates RPA1 at K163 to promote XPA recruitment and nucleotide excision repair.\",\n      \"evidence\": \"In vitro acetylation with site mapping, upstream kinase and eraser identification, and pathway-specific NER assays\",\n      \"pmids\": [\"28854354\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Selectivity for NER over other repair pathways mechanism not fully explained\", \"Single lab\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Defined a replication-fork function in which KAT2B acetylates H4K8 to recruit nucleases for fork degradation, with ATR phosphorylation at S264 acting as a brake relevant to PARPi resistance.\",\n      \"evidence\": \"Chromatin fractionation, in vitro H4K8 acetylation, phospho-site mapping, H4K8ac-binding domain analysis, and PARPi resistance assays\",\n      \"pmids\": [\"32966758\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How fork-localized KAT2B is initially recruited not fully defined\", \"Relevance across BRCA-proficient contexts not established\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Uncovered a HAT-independent cytoplasmic function, with KAT2B and GCN5 inhibiting TBK1 to negatively regulate IFN-\\u03b2, decoupling an immune role from histone acetylation.\",\n      \"evidence\": \"HAT-dead mutants, genetic knockout, cytoplasmic TBK1 inhibition, and IFN-\\u03b2 assays\",\n      \"pmids\": [\"25269644\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct biochemical mode of TBK1 inhibition not resolved\", \"Single lab\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How KAT2B's two catalytic activities (acetyltransferase and E3 ubiquitin ligase), its autoacetylation-controlled localization, and its many context-dependent substrates are coordinated and selected in a given cell remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No structural model integrating HAT and ubiquitin-ligase activities\", \"Substrate-selection rules in vivo undefined\", \"Functional separation from GCN5 across tissues incomplete\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0016740\", \"supporting_discovery_ids\": [7, 6, 0, 10, 24, 28, 36, 37]},\n      {\"term_id\": \"GO:0140096\", \"supporting_discovery_ids\": [0, 10, 24, 28, 31, 44, 36]},\n      {\"term_id\": \"GO:0016874\", \"supporting_discovery_ids\": [11, 26, 47]},\n      {\"term_id\": \"GO:0140110\", \"supporting_discovery_ids\": [1, 2, 13, 41]},\n      {\"term_id\": \"GO:0042393\", \"supporting_discovery_ids\": [6, 41]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [9, 8, 41]},\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [9, 42]},\n      {\"term_id\": \"GO:0000228\", \"supporting_discovery_ids\": [37, 34]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-74160\", \"supporting_discovery_ids\": [1, 2, 13, 41, 6]},\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [31, 44, 28, 34]},\n      {\"term_id\": \"R-HSA-73894\", \"supporting_discovery_ids\": [36, 37]},\n      {\"term_id\": \"R-HSA-1430728\", \"supporting_discovery_ids\": [27, 29]},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [25, 26, 10, 24]},\n      {\"term_id\": \"R-HSA-168256\", \"supporting_discovery_ids\": [42, 48]},\n      {\"term_id\": \"R-HSA-1266738\", \"supporting_discovery_ids\": [1, 53, 52]}\n    ],\n    \"complexes\": [\"STAGA/TFTC/ATAC\", \"cdk8-Mediator (T/G-Mediator)\", \"PRC2 (associated via EZH2)\"],\n    \"partners\": [\"EP300\", \"GCN5\", \"TP53\", \"MDM2\", \"GLI1\", \"MYOD1\", \"SMAD3\", \"SIRT1\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":9,"faith_total":9,"faith_pct":100.0}}